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At least 253 records · Page 14Linked to original sources
PubMed1997

Murine T cell determination of pregnancy outcome: I. Effects of strain, alphabeta T cell receptor, gammadelta T cell receptor, and gammadelta T cell subsets.

PROBLEM: T cells bearing alphabeta T cell receptor (TcR) and gammadelta TcR are present at the fetomaternal interface, and the latter, which express surface activation markers, can react with fetal trophoblast cell antigens. What is the role of these cells? METHOD: Using stress-abortion-prone DBA/2-mated CBA/J and abortion-resistant C57/B16 mice, alphabeta, gammadelta, and CD8+/- T cell subsets were measured in spleen and uterine decidua. The effect of immunization against abortion and administration of anti-TcR antibody in vivo was examined. Cytokine synthesis was measured by intracellular staining of Brefeldin A-treated cells. RESULTS: Abortion-prone matings showed an unexpected accumulation of gammadelta T cells beginning in the peri-implantation period and this was suppressed by immunization against abortion. The immunization deleted gammadelta T cells producing the abortogenic cytokines, TNF-alpha and gamma-interferon, and increased production of the anti-abortive cytokines, IL-10 and transforming growth factor-beta2 (TGF-beta2). Immunization also boosted the number of alphabeta T cells which were present in the decidua as early as 2 days after implantation. In vivo injection of GL4 (anti-delta) depleted gammadelta T cells producing Th1 cytokines in the peri-implantation period, and prevented abortions, whereas H57 (anti-beta) decreased the number of alphabeta T cells and led to 100% abortions. CD8+ T cells present in peri-implant decidua before onset of abortions were mostly alphabeta TcR+, although some were gammadelta+. Changes in gammadelta and alphabeta T cells in pregnancy were most dramatic in uterine tissue. CONCLUSION: Although decidual gammadelta T cells after formation of a distinct placenta and fetus produce anti-abortive TGF-beta2-like molecules and IL-10, prior events can lead to abortion. High local production of TNF-alpha and gamma-interferon develop during the peri-implantation phase because of an excessive increase in the Th1 cytokine+ subset of gammadelta cells; these cytokines may be contributed by other tissues in decidua, and the contribution of bioactive factors by gammadelta T cells may augment the cytokine pool. In contrast, alphabeta T cells (which may be inactivated by stress that causes abortions) may mediate the anti-abortive effect of alloimmunization. Alloimmunization involves a shift from a Th1 to a Th2 pattern in the gammadelta T cells in decidua.

Abortion, Spontaneous↗
PubMed2003

Retrovirus-mediated gene transfer in polyclonal T cells results in lower apoptosis and enhanced ex vivo cell expansion of CMV-reactive CD8 T cells as compared with EBV-reactive CD8 T cells.

To modulate alloreactivity after hematopoietic stem cell transplantation, "suicide" gene-modified donor T cells (GMCs) have been administered with an allogeneic T-cell-depleted marrow graft. We previously demonstrated that such GMCs, generated after CD3 activation, retrovirus-mediated transduction, and G418 selection, had an impaired Epstein-Barr virus (EBV) reactivity, likely to result in an altered control of EBV-induced lymphoproliferative disease. To further characterize the antiviral potential of GMCs, we compared the frequencies of cytomegalovirus (CMV)-specific CD8+ T (CMV-T) cells and EBV-specific CD8+ T (EBV-T) cells within GMCs from CMV- and EBV-double seropositive donors. Unlike anti-EBV responses, the anti-CMV responses were not altered by GMC preparation. During the first days of culture, CMV-T cells exhibited a lower level of CD3-induced apoptosis than did EBV-T cells. In addition, the CMV-T cells escaping initial apoptosis subsequently underwent a higher expansion rate than EBV-T cells. The differential early sensitivity to apoptosis could be in relation to the "recent activation" phenotype of EBV-T cells as evidenced by a higher level of CD69 expression. Furthermore, EBV-T cells were found to have a CD45RA-CD27+CCR7- effector memory phenotype, whereas CMV-T cells had a CD45RA+CD27-CCR7- terminal effector phenotype. Such differences could be contributive, because bulk CD8+CD27- cells had a higher expansion than did bulk CD8+CD27+ cells. Overall, ex vivo T-cell culture differentially affects apoptosis, long-term proliferation, and overall survival of CMV-T and EBV-T cells. Such functional differences need to be taken into account when designing cell and/or gene therapy protocols involving ex vivo T-cell manipulation.

Antigens, CD↗
PubMed2006

Porcine reproductive and respiratory syndrome virus (PRRSV) infection spreads by cell-to-cell transfer in cultured MARC-145 cells, is dependent on an intact cytoskeleton, and is suppressed by drug-targeting of cell permissiveness to virus infection.

BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is the etiologic agent of PRRS, causing widespread chronic infections which are largely uncontrolled by currently available vaccines or other antiviral measures. Cultured monkey kidney (MARC-145) cells provide an important tool for the study of PRRSV replication. For the present study, flow cytometric and fluorescence antibody (FA) analyses of PRRSV infection of cultured MARC-145 cells were carried out in experiments designed to clarify viral dynamics and the mechanism of viral spread. The roles of viral permissiveness and the cytoskeleton in PRRSV infection and transmission were examined in conjunction with antiviral and cytotoxic drugs. RESULTS: Flow cytometric and FA analyses of PRRSV antigen expression revealed distinct primary and secondary phases of MARC-145 cell infection. PRRSV antigen was randomly expressed in a few percent of cells during the primary phase of infection (up to about 20-22 h p.i.), but the logarithmic infection phase (days 2-3 p.i.), was characterized by secondary spread to clusters of infected cells. The formation of secondary clusters of PRRSV-infected cells preceded the development of CPE in MARC-145 cells, and both primary and secondary PRRSV infection were inhibited by colchicine and cytochalasin D, demonstrating a critical role of the cytoskeleton in viral permissiveness as well as cell-to-cell transmission from a subpopulation of cells permissive for free virus to secondary targets. Cellular expression of actin also appeared to correlate with PRRSV resistance, suggesting a second role of the actin cytoskeleton as a potential barrier to cell-to-cell transmission. PRRSV infection and cell-to-cell transmission were efficiently suppressed by interferon-gamma (IFN-gamma), as well as the more-potent experimental antiviral agent AK-2. CONCLUSION: The results demonstrate two distinct mechanisms of PRRSV infection: primary infection of a relatively small subpopulation of innately PRRSV-permissive cells, and secondary cell-to-cell transmission to contiguous cells which appear non-permissive to free virus. The results also indicate that an intact cytoskeleton is critical for PRRSV infection, and that viral permissiveness is a highly efficient drug target to control PRRSV infection. The data from this experimental system have important implications for the mechanisms of PRRSV persistence and pathology, as well as for a better understanding of arterivirus regulation.

Animals↗
PubMed1996

Enhanced E-cadherin expression and increased calcium-dependent cell-cell adhesion in human T-cell leukemia virus type I Tax-expressing PC12 cells.

Human T-cell leukemia virus type I (HTLV-I) Tax protein induces the expression of host cellular genes, some of which are crucial in cell proliferation and differentiation. We examined the mechanisms by which HTLV-I Tax protein induces phenotypic changes in PC12 cells. We demonstrated that the HTLV-I Tax gene induces epithelioid changes and increases cell-cell contact in PC12 cells. No change in the expression of the neural cell adhesion molecule was observed between HTLV-I Tax-expressing PC12 cells and PC12 cells transfected with a control plasmid. However, HTLV-I Tax-expressing PC12 cells demonstrated a marked change in the abundance and distribution of E-cadherin, which was concentrated at regions of cellular contact and accompanied by changes in calcium-dependent cell adhesion. Although E-cadherin is expressed at low levels in PC12 and PC12 transfected with a control plasmid cells, the steady state level of E-cadherin in tax-expressing PC12 cells increases significantly, apparently as a result of regulation at the transcriptional level. Diminished expression of Tax protein in Tax-expressing PC12 cells exposed to antisense oligonucleotides for the Tax gene suppresses E-cadherin expression and decreases cell-cell adhesion. These findings imply that HTLV-I Tax protein enhanced E-cadherin expression modulates calcium-dependent cell-cell adhesion mechanisms.

Animals↗
PubMed1998

TPA-induced cohort migration of well-differentiated human rectal adenocarcinoma cells: cells move in a RGD-dependent manner on fibronectin produced by cells, and phosphorylation of E-cadherin/catenin complex is induced independently of cell-extracellular matrix interactions.

We have already presented a two-dimensional cell motility assay using a highly metastatic variant (L-10) of human rectal adenocarcinoma cell line RCM-1 as a motility model of tumour cells of epithelial origin. In this model, L-10 cells showed locomotion as a coherent sheet when stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA), and we called this type of movement "cohort migration". Electron and immunoelectron microscopic study of the migrating cell sheets demonstrated localized release from cell-cell adhesion only at the lower portion of the cells with loss of E-cadherin immunoreactivity, and this change was associated with increased tyrosine phosphorylation of the E-cadherin-catenin complex, including beta-catenin. Cell-extracellular matrix (ECM) interactions involved in this TPA-induced cohort migration and their effect on tyrosine phosphorylation of the E-cadherin-catenin complex have now been investigated. L-10 cell cohort migration was almost completely inhibited by addition of Arg-Gly-Asp (RGD) peptide into the medium, and thus RGD dependent. Cohort migration was stimulated on type I and IV collagens, fibronectin (FN)- and laminin-coated substratum, but was inhibited by RGD only on FN-coated surface. By using immunofluorescent techniques, FN was demonstrated preferentially around migrating cells, and a protein synthesis inhibitor, cycloheximide, inhibited the migration by about 75%. FN produced by L-10 cells were found to be mostly EDA+ FN when analysed by RT-PCR. Moreover, anti-FN antibody, but not anti-vitronectin antibody, inhibited the TPA-induced cohort migration almost completely. Thus, it was likely that L-10 cells produced FN themselves and moved on the FN substrate in an RGD-dependent manner. However, stimulation of migration by type I collagen coating and inhibition by RGD treatment did not affect the tyrosine phosphorylation of the E-cadherin-catenin complex induced by TPA, indicating that cell-cell interactions were adjusted to suit cell migration, irrespective of the condition of cell-ECM adhesion, during TPA-induced cohort migration.

Adenocarcinoma↗
PubMed2004

The characteristics of human NKT cells in lung cancer--CD1d independent cytotoxicity against lung cancer cells by NKT cells and decreased human NKT cell response in lung cancer patients.

The activation of human Valpha24+Vbeta11+natural killer T cells (NKT) cells (Valpha24 NKT cells) induces effective antitumor responses with secondary immune effects through activation of conventional T cells and natural killer cells. In this study, we attempted to analyze the characteristics of human NKT cells in lung cancer patients. Valpha24 NKT cells stimulated with alpha-GalCer from healthy volunteers exhibited direct cytotoxic activity against two (RERF-LC-OK and PC-3) of seven human lung cancer cell lines studied. Cytotoxicity by Valpha24 NKT cells against human lung cancer cells was dependent on the perforin pathway and independent of Fas/FasL pathway. Intracellular adhesion molecule (ICAM)-1 expression on tumor cells was clearly associated with the cytotoxicity of Valpha24 NKT cells. On the other hand, the proportion of Valpha24 NKT cells in the patients with lung cancer was lower than that in the healthy volunteers. Furthermore, the proliferative response of Valpha24 NKT cells to alpha-GalCer was significantly lower in the peripheral blood mononuclear cells in the patients with lung cancer. Addition of granulocyte colony-stimulating factor moderately restored the low proliferative response of Valpha24 NKT cells in the patients with lung cancer, however the percentage by which the response was restored in these patients was still lower than the natural response in healthy volunteers. These results suggest that Valpha24 NKT cells may play a pivotal role or the antitumor response in lung cancer.

Adult↗
PubMed2003

Dendritic cells loaded with apoptotic tumour cells induce a stronger T-cell response than dendritic cell-tumour hybrids in B-CLL.

Dendritic cells (DC) are professional (specialised) antigen-presenting cells that can capture antigen from apoptotic tumour cells and induce MHC class I- and II-restricted responses. Also, DC fused with tumour cells may be effective for immune response induction. Both cell preparations may be considered as vaccine candidates in a therapeutic approach. We examined autologous T-cell activation by DC that had endocytosed leukaemic B-cell apoptotic bodies (Apo-DC) and compared it to the T-cell stimulatory capacity of DC that were fused with tumour cells. Following incubation, 22.6+/-6.2 (mean+/-s.e.m.) of DC had endocytosed leukaemic cells, while the frequency of DC-leukaemic cell hybrids was 10.5+/-2.6%. Apo-DC and hybrid cells both demonstrated the ability to stimulate a tumour-specific T-cell immune response in vitro. A T-cell proliferation response was also observed in four out of five CLL patients when using Apo-DC. However, fusion hybrids lacked the ability to elicit a proliferative response. Apo-DC also induced an IFN-gamma response, as did hybrid cells. The cytokine response induced by Apo-DC was significantly higher than that induced by fusion (P<0.05). This study shows that endocytosed apoptotic tumour cells induced a significantly stronger T-cell response than DC hybrids; and as such should be a better candidate for vaccine production.

Adult↗
PubMed1992

Immunoregulatory functions for murine intraepithelial lymphocytes: gamma/delta T cell receptor-positive (TCR+) T cells abrogate oral tolerance, while alpha/beta TCR+ T cells provide B cell help.

Past work has shown that a subset of effector T cells with unique characteristics could abrogate hapten- or antigen-induced tolerance, and the reconstitution of this immune response has been termed contrasuppression. We have studied contrasuppression in a model of oral tolerance (OT) in which adoptively transferred antigen-specific T contrasuppressor (Tcs) cells reverse OT and result in antibody responses to the eliciting antigen. In the present study, we show that murine intraepithelial lymphocytes (IELs) from mice orally immunized with sheep red blood cells (SRBC) contain T cells that exhibit Tcs cell activity. This effect was mediated by CD3+ gamma/delta T cell receptor-positive (TCR+), but not alpha/beta TCR+ T cells, and gamma/delta TCR+ Tcs cells were associated with both the CD4-,CD8+ and CD4-,CD8- (double-negative) IEL fractions. The CD4-,CD8+ gamma/delta TCR+ IELs were further separated into Vicia villosa-adherent and -nonadherent fractions. Adoptive transfer of V. villosa-adherent gamma/delta TCR+ T cells to mice with OT to SRBC resulted in splenic IgA, IgM, and IgG subclass anti-SRBC responses, while V. villosa-nonadherent gamma/delta TCR+ T cells were without activity. The gamma/delta TCR+ IELs did not support in vitro antibody responses in B cell cultures, while alpha/beta TCR+ IELs were effective T helper cells. Further, cytokine production by the gamma/delta TCR+ IELs was examined, and the gamma/delta TCR+ V. villosa-adherent fraction, which possessed contrasuppressor function, contained low levels of IL-5 mRNA and small numbers of IL-5-producing cells when compared with alpha/beta TCR+ IELs and V. villosa-nonadherent gamma/delta TCR+ IELs. Our results now show that mouse IELs contain two distinct types of T cells that function in the immune response, e.g., alpha/beta TCR+ T cells that produce IL-5 and function as helper cells, and gamma/delta TCR+ T cells that restore antibody responses in mice that had been orally tolerized with antigen.

Animals↗
PubMed2004

HIV-infected Langerhans cells preferentially transmit virus to proliferating autologous CD4+ memory T cells located within Langerhans cell-T cell clusters.

Langerhans cells (LC) are likely initial targets for HIV following sexual exposure to virus and provide an efficient means for HIV to gain access to lymph node T cells. The purpose of this study was to examine the nature of the CD4(+) T cell that becomes infected by HIV-infected LC. We infected human LC within tissue explants ex vivo and then, 3 days later, cocultured HIV-infected LC with different subsets of autologous CD4(+) T cells. Using multicolor flow cytometric analyses of LC-CD4(+) T cell cocultures, we documented that HIV-infected LC preferentially infected memory (as compared with naive) CD4(+) T cells. Proliferating and HIV-infected CD4(+) memory T cells were more frequently detected in conjugates of LC and autologous CD4(+) T cells, suggesting that T cells become activated and preferentially get infected through cluster formation with infected LC, rather than getting infected with free virus produced by single HIV-infected LC or T cells. p24(+) Memory CD4(+) T cells proliferated well in the absence of superantigen; by contrast, p24(+) T cells did not divide or divided only once in the presence of staphylococcal enterotoxin B, suggesting that virus production was rapid and induced apoptosis in these cells before significant proliferation could occur. These results highlight that close interactions between dendritic cells, in this case epidermal LC, and T cells are important for optimal HIV replication within specific subsets of CD4(+) T cells. Disrupting cluster formation between LC and memory CD4(+) T cells may be a novel strategy to interfere with sexual transmission of HIV.

Antigens, Bacterial↗
PubMed2005

Vaccination of dendritic cells loaded with interleukin-12-secreting cancer cells augments in vivo antitumor immunity: characteristics of syngeneic and allogeneic antigen-presenting cell cancer hybrid cells.

Cancer immunotherapy by fusion of antigen-presenting cells and tumor cells has been shown to induce potent antitumor immunity. In this study, we characterized syngeneic and allogeneic, murine macrophage/dendritic cell (DC)-cancer fusion cells for the antitumor effects. The results showed the superiority of allogeneic cells as fusion partners in both types of antigen-presenting cells in an in vivo immunotherapy model. A potent induction of tumor-specific CTLs was observed in these immunized conditions. In addition, the immunization with DC-cancer fusion cells was better than that with macrophage-cancer fusion cells. Both syngeneic and allogeneic DC-cancer fusion cells induced higher levels of IFN-gamma production than macrophage-cancer fusion cells. Interestingly, allogeneic DC-cancer fusion cells were superior in that they efficiently induced Th1-type cytokines but not the Th2-type cytokines interleukin (IL)-10 and IL-4, whereas syngeneic DC-cancer fusion cells were powerful inducers of both Th1 and Th2 cytokines. These results suggest that allogeneic DCs are suitable as fusion cells in cancer immunotherapy. To further enhance the antitumor immunity in the clinical setting, we prepared DCs fused with IL-12 gene-transferred cancer cells and thus generated IL-12-secreting DC-cancer fusion cells. Immunization with these gene-modified DC-cancer fusion cells was able to elicit a markedly enhanced antitumor effect in the in vivo therapeutic model. This novel IL-12-producing fusion cell vaccine might be one promising intervention for future cancer immunotherapy.

Animals↗
PubMed1993

E-selectin and vascular cell adhesion molecule-1 mediate adult T-cell leukemia cell adhesion to endothelial cells.

We studied the adhesion properties of peripheral blood leukemic cells from 10 patients with adult T-cell leukemia (ATL) to endothelial cells to better understand the mechanism of leukemic cell infiltration. ATL cells expressed lymphocyte function-associated antigen-1 (LFA-1), but the expression of very late antigen-4 (VLA-4) and sialyl-Lewisx (SLex) was variable. They did not express sialyl-Lewisa (SLea). Cell adhesion assays, which were performed in nine patients, showed marked adhesion of ATL cells to interleukin [IL]-1-activated human umbilical vein endothelial cells (HUVEC). A monoclonal antibody (MoAb) against E-selectin consistently inhibited ATL cell adhesion, and an MoAb against vascular cell adhesion molecule-1 (VCAM-1) or an MoAb against VLA-4 sometimes diminished it. In contrast, an MoAb against LFA-1 had a minor effect on freshly isolated ATL cell adhesion to HUVEC. The percentage of SLex+ cells in the cell population adherent to IL-1-activated HUVEC was slightly higher than that in unseparated cells. These results, together with the detection of E-selectin expression on the endothelium at ATL skin lesions, indicate that E-selectin-mediated adhesion is the major pathway for the adherence of ATL cells to endothelial cells. In addition, the ligand for E-selectin on ATL cells appears to differ from that on neutrophils.

Antibodies, Monoclonal↗
PubMed1999

Single adult human CD34(+)/Lin-/CD38(-) progenitors give rise to natural killer cells, B-lineage cells, dendritic cells, and myeloid cells.

Marrow stromal cultures support adult CD34(+)/Lin-/HLA-DR- or CD34(+)/Lin-/CD38(-) cell differentiation into natural killer (NK) or myeloid cells, but unlike committed lymphoid progenitors (CD34(+)/Lin-/CD45RA+/CD10(+)), no B cells are generated. We tested whether different microenvironments could establish a developmental link between the NK and B-cell lineages. Progenitors were cultured in limiting dilutions with interleukin-7 (IL-7), flt3 ligand (FL), c-kit ligand (KL), IL-3, IL-2, and AFT024, a murine fetal liver line, which supports culture of transplantable murine stem cells. NK cells, CD10(+)/CD19(+) B-lineage cells and dendritic cells (DC) developed from the same starting population and IL-7, FL, and KL were required in this process. Single cell deposition of 3,872 CD34(+)/Lin-/CD38(-) cells onto AFT024 with IL-7, FL, KL, IL-2, and IL-3 showed that a one time addition of IL-3 at culture initiation was essential for multilineage differentiation from single cells. Single and double lineage progeny were frequently detected, but more importantly, 2% of single cells could give rise to at least three lineages (NK cells, B-lineage cells, and DC or myeloid cells) providing direct evidence that NK and B-lineage differentiation derive from a common lymphomyeloid hematopoietic progenitor under the same conditions. This study provides new insights into the role of the microenvironment niche, which governs the earliest events in lymphoid development.

ADP-ribosyl Cyclase↗
PubMed1985

Accessory role of autologous T lymphocytes and adherent cells for the in vitro proliferation of T-cell colony-forming cells from patients with T-cell acute lymphoblastic leukemia.

Peripheral blood T colony-forming cells (T-CFC) from patients with T-cell malignancies can proliferate in methylcellulose in the absence of added growth factors or mitogenic stimulation. Mononuclear cells (MNC) from 7 patients with T-cell acute lymphoblastic leukemia were separated into cells forming rosettes with sheep erythrocytes (E+) or not (E-). E- cells were further depleted by complement-mediated cytotoxicity with OKT3 monoclonal antibody (E-OKT3- cells). The study of their spontaneous T-cell colony-forming ability suggested that proliferation of T-CFC in the absence of added growth factors requires cellular cooperation because: (1) No colony growth was observed at low cell concentrations (up to 2 X 10(4) cells/ml) whereas at higher cell densities the number of colonies increased exponentially; (2) The plating efficiency from unfractionated MNC was higher than that from E-OKT3- or E+ cells. Irradiated autologous E+ cells enhanced the plating efficiency from blast-enriched cell fractions (E-OKT3-) when co-cultured either directly in methylcellulose or separately in a two layer assay (agar-methylcellulose), suggesting that their activity could be due to diffusible factors; (3) Adherent-cell depletion of MNC decreased colony formation. Autologous irradiated adherent cells were able to restore the plating efficiency from MNCA- cells when co-cultured directly in methylcellulose but not in separate layers; however, media conditioned by patients' A+ cells could enhance the colony growth from patients' MNCA- cells, indicating that their activity could also be mediated by constitutively released soluble factors.

Antibodies, Monoclonal↗
PubMed1992

Cells and mediators involved in immunoglobulin synthesis by human circulating mononuclear cells. IV. B cells synthesize but do not secrete immunoglobulins because of a defect in the non-T non-B (null) cells.

Null cells (non-T and non-B lymphocytes) have previously been demonstrated to be obligatory participants for immunoglobulin synthesis and secretion by normal B cells in culture. Normal null cells have been demonstrated to secrete a factor, human immunoglobulin synthesis/secretion-facilitating factor (HISFF), which can replace the null cells in the culture. In this investigation, the B cells of an 8-month-old male infant and a 46-year-old male adult who presented with a humoral (antibody) immunodeficiency syndrome synthesized immunoglobulin but did not secrete immunoglobulin after culture with pokeweed mitogen and autologous T cells, monocytes, and null cells. In contrast, the patients' B cells synthesized and secreted immunoglobulin after the addition of allogeneic normal null cells or HISFF to the cultures. The same results were obtained with the cells of the infant and the adult patient tested at monthly intervals for 4 months. The results demonstrate that the patients' T cells, B cells, and monocytes functioned normally and that only the patients' null cells were defective. These findings provide an explanation for the absence of immunoglobulin in the circulation of "non(immunoglobulin)secretors," although they possess normal numbers of circulating immunoglobulin-synthesizing B cells. The defect is in the null cell and not in the B cell and consists of the inability of the null cell to secrete HISFF that facilitates the synthesis and secretion of immunoglobulin by the B cell.

Antigens, CD↗
PubMed1971

Cell-to-cell interaction in the immune response. VI. Contribution of thymus-derived cells and antibody-forming cell precursors to immunological memory.

Collaboration between thymus-derived lymphocytes and nonthymus-derived antibody-forming cell precursors occurs in the primary antibody response of mice to heterologous erythrocytes and serum proteins. The purpose of the experiments reported here was to determine whether collaboration took place in an adoptive secondary antibody response. A chimeric population of lymphocytes was produced by reconstituting neonatally thymectomized CBA mice soon after birth with (CBA x C57BL)F(1) thymus lymphocytes. These mice could be effectively primed to fowl immunoglobulin G (FgammaG) and their thoracic duct lymphocytes adoptively transferred memory responses to irradiated mice. The activity of these cells was impaired markedly by preincubation with CBA anti-C57BL serum and to a lesser extent by anti-theta-serum. Reversal of this deficiency was obtained by adding T cells in the form of thoracic duct cells from normal CBA mice. Cells from FgammaG-primed mice were at least 10 times as effective as cells from normal mice or from CBA mice primed to horse erythrocytes. These results were considered to support the concept that memory resides in the T cell population and that collaboration between T and B cells is necessary for an optimal secondary antibody response. Poor antibody responses were obtained in irradiated mice given mixtures of thoracic duct cells from primed mice and of B cells from unprimed mice (in the form of spleen or thoracic duct cells from thymectomized donors). In contrast to the situation with T cells, the deficiency in the B cell population could not be reversed by adding B cells from unprimed mice. It was considered that memory resides in B cells as well as in T cells and that priming probably entails a change in the B cell population which is fundamentally different from that produced in the T cell population.

Animals↗
PubMed1975

Expression of T-cell differentiation antigens on effector cells in cell-mediated cytotoxicity in vitro. Evidence for functional heterogeneity related to the surface phenotype of T cells.

The cell-mediated cytotoxicity (CMC) of nonadherent cells from the peritoneal cavity (NAPC) of alloimmunized mice can be measured by the [3H]proline microassay. The exhibition of thymus-derived (T) cell antigens on these killer cells was studied by incubating them with the relevant T-cell antisera and complement (C), under optimal conditions for lysis, before performance of the CMC assay. Under these conditions, the following T-cell antigens were demonstrable on the killer population in terms of percent reduction in CMC by the respective antisera: (a) Thy-1.1 (83%) and Thy-1.2 (100%), (b) MSLA (86%), (c) NTA-RA (a T-cell antigen recognized by naturally occurring autoantibody of NZB mice) (62%), (d) Ly1.1 )58%, (e) Ly-2.1 (11%; considered a marginal result) and Ly-2.2 (63%), and (f) Ly-3.2 (77%). The following were not demonstrable: (g) TL, and (h) Ly-1.2. (i) The antigen Ly-3.1 was not studied. Omission of C deprived all T-cell antisera tested of their capacity to suppress CMC, indicating that the cell components recognized by such antisera may perform no direct function in CMC. On the assumption that all Ly+ cells are Thy-1+, it is clear that the T-cell members of the immune NAPC population must be heterogenous. This follows from the fact that the proportions of T cells lysed by different Ly antisera did not correspond with ensuing degree of loss of CMC capacity. The extremes were represented by anti-Ly-1.2 (74% Thy-1+ cells lysed, but no reduction in CMC) and Ly-3.2 (54% Thy-1+ cells lysed, with 77% reduction in CMC). From this initial survey it appears that the C57BL/6 mice killer T-cell population active in CMC in vitro is relatively rich in surface antigens of the Ly-2/Ly-3 category and relatively poor in representation of the Ly-1 surface antigens. It remains to be seen whether this killer cell phenotype, poor in Ly-1 and rich in Ly-2/Ly-3, is characteristic of the mouse generally. From these results it appears that subsets of T cells with different immunological functions may exhibit qualitative or quantitative differences in surface antigens specified by different Ly loci; this will be easier to assess in the future when the results of experiments with the same Ly antisera but dealing with T-cell functions other than CMC become available.

Animals↗
PubMed1999

Vascular cell apoptosis: cell type-specific modulation by transforming growth factor-beta1 in endothelial cells versus smooth muscle cells.

BACKGROUND: It is postulated that vascular lesion formation and remodeling involves a balance between vascular cell death and cell proliferation. Transforming growth factor-beta1 (TGF-beta1) is a pleiotropic factor expressed within vascular cells that regulates cell growth in a tissue-specific manner. This study tested the hypothesis that the control of vascular cell apoptosis involves cell type-specific regulation by TGF-beta1. METHODS AND RESULTS: In response to serum withdrawal, cultured endothelial cells and vascular smooth muscle cells exhibited apoptosis as evidenced by DNA laddering and quantitated by analysis of nuclear chromatin morphology. Addition of TGF-beta1 to endothelial cells in serum-free media further potentiated the induction of apoptosis in a dose-dependent fashion. Moreover, TGF-beta1 promoted endothelial cell death despite the presence of 10% serum. However, endothelial cells plated on collagen I were resistant to TGF-beta1-induced apoptosis. This antiapoptotic influence of the matrix was mimicked by integrin activation with anti-beta1 antibodies and associated with increased expression of the antiapoptotic factor bcl-2. In accord with the hypothesis that the modulation of antiapoptotic gene expression may mediate the effects of TGF-beta1 and beta1 integrins on cell fate, we observed that endothelial cells with constitutive upregulation of bcl-2 remained viable despite exposure to TGF-beta1 in serum-free conditions. In contrast to the proapoptotic effect of TGF-beta1 in endothelial cells, addition of TGF-beta1 to vascular smooth muscle cells in serum-free media inhibited apoptosis. CONCLUSIONS: These findings suggest that the effect of cytokines such as TGF-beta1 on cell fate is contextual and is modulated by cell-matrix interactions in a cell type-specific manner.

Animals↗
PubMed1991

[Immunohistological study of the nasal mucosa in allergic rhinitis with reference to B cell, T cell subpopulation, activated T cell and Langerhans cell].

Distribution of B lymphocytes, T lymphocytes subpopulations, activated T lymphocytes and Langerhans cells of the nasal mucosa in 28 patients with nasal allergy ranging in age from 19 years to 54 years was studied. The specimens from inferior turbinates were frozen at -70 degrees C and sliced at a thickness of 4 microns by cryostat. Monoclonal antibodies and peroxidase-antiperoxidase staining (Ortho) were used to detect these cells. OKT4, OKT8, OKT6 and OKB19 were used as markers of helper/inducer T cells, suppresser/cytotoxic T cells, Langerhans cells and B cells, respectively. OKDR was used as a marker of activated T cells, B cells, Langerhans cells and macrophages. Many OKT4 and OKT8 positive cells were observed in lamina propria. In every case, more OKT4 positive cells were detected in number than OKT8 positive cells. Some OKB19 positive cells and macrophages were observed in lamina propria, but OKT6 positive cells were not observed. OKDR positive cells were observed in high density, and more OKDR positive cells were detected than OKT4, OKT8 and OKB19 positive cells. Most of the OKDR positive cells were small in size and round in shape. From these results, many T lymphocytes were thought to be activated, and T lymphocytes were thought to play an important role in nasal allergy.

Adult↗