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At least 55 records · Page 3Linked to original sources
PubMed2006

The frequency of B- and T-cell gene rearrangements and epstein-barr virus in T-cell lymphomas: a comparison between angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified with and without associated B-cell proliferations.

We report on a series of 58 cases of angioimmunoblastic T-cell lymphoma (AILT) and 59 cases of peripheral T-cell lymphoma, unspecified (PTCL-NOS). Subsets of cases from both diagnostic groups were complicated by associated B-cell proliferations, and we performed B- and T-cell clonality studies and in situ hybridization for Epstein-Barr virus (EBV) to investigate the relationship between B-cell proliferation, B-cell clonality, and EBV. Using multiplex polymerase chain reaction assays based on the BIOMED-2 collaborative study, we detected TCRgamma T-cell clones in 78 and 81% of AILT and PTCL-NOS cases, respectively, and IGH B-cell clones in 34 and 35% of AILT and PTCL-NOS cases, respectively. The majority of cases contained EBV-positive cells, including 50% of AILT and 57% of PTCL-NOS cases, and cases with B-cell proliferations were more often EBV-positive. Although a relatively high rate of B-cell clonality has been shown for AILT, our findings for PTCL-NOS differ from previous reports in that B-cell clonality was relatively frequent. Overall, a positive B-cell clone correlated, in part, with the presence of a B-cell proliferation but not with EBV. Our findings demonstrate that B-cell clonality is a common finding in AILT and PTCL-NOS, and its presence should not negate the diagnosis established by morphologic, immunophenotypic, and clinical findings.

Cell Proliferation↗
PubMed1990

Cells and mediators which participate in immunoglobulin synthesis by human mononuclear cells. III. Null cells secrete a factor(s) (human immunoglobulin synthesis/secretion-facilitating factor) that can replace the null cells in the synthesis of immunoglobulin by cultured B cells.

In the accompanying communication, it was demonstrated that the null cells, the TM cells, monocytes and PWM are all obligatory participants in the synthesis and secretion of immunoglobulins by human B cells in culture. Here we demonstrate that the null cells secrete a factor, referred to as human immunoglobulin synthesis/secretion-facilitating factor (HISFF) that can replace the null cells in the cultures. HISFF is distinct from the known T cell-derived interleukins. HISFF functions in an HLA-unrestricted fashion since it can facilitate the synthesis and secretion of immunoglobulins by allogeneic B cells. The null cells cultured with TM helper cells and PWM required monocytes in the culture in order to secrete HISFF. Furthermore, B cells cultured with TM cells in medium containing HISFF, monocyte-derived factors and PWM nevertheless required monocytes in order to respond to the HISFF signal. Thus, the monocyte plays a pivotal role in the secretion of and response to HISFF. Normal levels of immunoglobulin were synthesized even when HISFF was added to the cultures of B cells, TM cells and monocytes, in the presence of PWM, as late as day 6 of the 7 day culture. We conclude that the null cells participate in immunoglobulin synthesis by the B cells by secreting a soluble mediator, HISFF, capable of replacing the null cells in the culture; and that the HISFF signal is the last signal received by the B cell before it begins to synthesize and secrete immunoglobulins.

B-Lymphocytes↗
PubMed2000

Modeling HIV transfer between dendritic cells and T cells: importance of HIV phenotype, dendritic cell-T cell contact and T-cell activation.

OBJECTIVE: To study the requirements for HIV transfer between dendritic cells (DC) and CD4 T cells, using an in vitro model, combined with flow cytometry. METHODS: Immature DC and macrophages (MA) were generated from monocytes. After infection, DC or MA were cultured alone or with purified CD4 T cells. Intracellular HIV was measured, using (1) the monocyte (MO)-tropic AD8 HIV, endowed with enhanced green fluorescent protein (EGFP); and (2) intracellular staining of laboratory HIV strains and clones from primary isolates. RESULTS: (1) Clone AD8-EGFP infected DC and MA with equal efficiency, but the virus was preferentially transferred from DC to autologous T cells. (2) DC were more productively infected with R5/NSI, as compared to X4/SI, HIV, but both HIV phenotypes were easily transmitted to autologous T4 cells. (3) HIV-infected DC transferred the virus to T cells across a semi-permeable membrane, if the T cells were in contact with non-infected DC. (4) Co-culture of T cells with autologous non-infected DC induced T-cell activation. HIV-infected DC selectively increased HLA-DR on T cells and HLA-DR (+) T cells were preferential targets for HIV transfer. (5) Resting Ba-L-infected CD4 T cells were able to transmit the virus 'inversely' to co-cultured DC. CONCLUSION: HIV transfer between monocyte-derived dendritic cells and autologous CD4 T cells was directly demonstrated using flow cytometry. The transfer proceeded in both directions, depended on cellular contact and was associated with partial T-cell activation. This model, representing relevant in vivo targets of HIV, is useful to further investigate interactions between HIV, DC and T cells, without the need for primary ex vivo DC.

CD4-Positive T-Lymphocytes↗
PubMed1998

Role of the liver in T cell differentiation--generation of CD3-CD4+/CD8+TCRbeta- cells and CD3-4-8-TCRbeta+ cells from CD4-8-TCRbeta- athymic nude bone marrow cells by culture with parenchymal liver cells.

To investigate the influence of the liver on differentiation of hematopoietic stem cells/pro-T cells, TN-NWP-BMC (athymic nude bone marrow cells that were treated with anti-TCRbeta, anti-CD4, and anti-CD8 Abs plus complement and then passed through a nylon wool column) were cultured on parenchymal liver cells. After culture for 2.5 days, CD3-4-8-TCRbeta+ cells and CD3-CD4+/CD8+TCRbeta- cells were developed from TN-NWP-BMC. TCRVbeta8+ cells comprised 19.9% of CD3-4-8-TCRbeta+ cells, and Vbeta8 mRNA was detected in the CD3-4-8-TCRbeta+ cells by reverse transcriptase-polymerase chain reaction. The CD3-CD4+/CD8+TCRbeta- cells contained not only single-positive cells but also CD4+8+ double-positive cells. The CD8 protein consisted of 88.9% CD8alpha+beta-, 10.1% CD8alpha+beta+, and 1% CD8alpha-beta+ molecules. From these results and the finding of co-expressed antigens, CD3-4-8-TCRbeta+ cells and CD3-CD4+/CD8+TCRbeta- cells appear to be immature cells not committed to a certain cell lineage.

Animals↗
PubMed2003

Non-small and small cell lung carcinoma cell lines exhibit cell type-specific sensitivity to edelfosine-induced cell death and different cell line-specific responses to edelfosine treatment.

The unique signal transduction pathways that distinguish non-small cell lung carcinoma (NSCLC) from small cell lung carcinoma (SCLC) are poorly understood. We investigated the ability of edelfosine, an inhibitor of phosphatidylinositol-specific phospholipase C (PLC) to inhibit cell viability among four NSCLC cell lines and four SCLC cell lines. The differential sensitivity of cells to edelfosine's cytostatic and cytotoxic effects has been attributed to edelfosine-induced changes in the activities of many enzymes, including c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinases (ERK), p38 kinase, and poly(ADP-ribose) polymerase (PARP). To investigate the role of these enzymes in edelfosine-induced cytotoxicity, we correlated edelfosine-induced changes in enzyme activity and cell viability among the different NSCLC and SCLC cell lines. We found that NSCLC cells are much more susceptible to the cytotoxic effects of this drug than are SCLC cells. Three out of the four edelfosine-sensitive NSCLC cell lines (NCI-H157, NCI-H520, NCI-H522) exhibit G2/M arrest, significant apoptosis and some degree of JNK activation in response to drug treatment. In contrast, none of the SCLC cell lines exhibit edelfosine-induced G2/M arrest or significant apoptosis. A comparison of the edelfosine-induced effects among the sensitive and resistant lung cancer lines indicates that there is little correlation between edelfosine-induced cytotoxicity and altered activities of JNK, ERK, p38, or cleavage of PARP. These results demonstrate that edelfosine-induced changes in JNK, ERK, p38, or PARP are not good predictors of cell susceptibility to edelfosine-induced cytotoxicity. Thus, edelfosine-induced inactivation of PLC may disrupt signaling cascades downstream of PLC that are unique to individual cellular environments. These findings also identify edelfosine as one of the few potential chemotherapeutic agents that has a greater cytotoxic effect against NSCLC cells than SCLC cells.

Antineoplastic Agents↗
PubMed2004

Regulatory T cells can migrate to follicles upon T cell activation and suppress GC-Th cells and GC-Th cell-driven B cell responses.

How Tregs migrate to GCs, and whether they regulate the helper activity of the T cells in GCs (GC-Th cells) remains poorly understood. We found a T cell subset in human tonsils that displays potent suppressive activities toward GC-Th cell-dependent B cell responses. These Tregs with the surface phenotype of CD4+CD25+CD69- migrate well to CCL19, a chemokine expressed in the T cell zone, but poorly to CXCL13, a chemokine expressed in the B cell zone. This migration toward the T cell-rich zone rapidly changes to trafficking toward B cell follicles upon T cell activation. This change in chemotactic behavior upon activation of T cells is consistent with their switch in the expression of the 2 chemokine receptors CXCR5 and CCR7. CD4+CD25+CD69- Tregs suppress GC-Th cells and GC-Th cell-induced B cell responses such as Ig production, survival, and expression of activation-induced cytosine deaminase. Our results have identified a subset of Tregs that is physiologically relevant to GC-Th cell-dependent B cell responses and a potential regulation mechanism for the trafficking of these Tregs to GCs.

Antigens, CD↗
PubMed1985

B-cell growth factor (B-cell growth factor I or B-cell-stimulating factor, provisional 1) is a differentiation factor for resting B cells and may not induce cell growth.

B-cell growth factor I [BCGF I or B-cell-stimulating factor, provisional 1 (BSFp1)] has been defined as a T-cell-derived lymphokine that acts as a co-stimulator of polyclonal B-cell growth in B cells cultured with anti-mu, anti-delta, or anti-Ig. Based on a number of studies it has been suggested that anti-Ig induces cell enlargement, entry into the G1 phase of the cell cycle, and expression of receptors for BSFp1. BSFp1 then induces entry of the cells into S phase. By adding BSFp1 prior to anti-Ig, we have found evidence that BSFp1 renders cells susceptible to anti-Ig-mediated entry of cells into G2/S phase. In contrast, if cells are first treated with anti-Ig, washed, and then cultured with BSFp1, they do not enter S phase. Taken together, these results suggest that BSFp1 acts on the resting B cells not as a growth factor but rather as a lymphokine that prepares cells for anti-Ig-mediated activation. Taken together with previous reports that BSFp1 induces increased expression of Ia antigens on resting B cells, these studies suggest that BSFp1 may be a differentiation factor rather than a growth factor and that it acts on resting B cells.

Animals↗
PubMed1988

Analysis of two distinct B cell activation pathways mediated by a monoclonal T helper cell. II. T helper cell secretion of interleukin 4 selectively inhibits antigen-specific B cell activation by cognate, but not noncognate, interactions with T cells.

A single monoclonal T helper (Th) clone can activate B cells in two distinct pathways; a cognate pathway requiring a major histocompatibility complex (MHC)-restricted T-B cell interaction, and a noncognate pathway not requiring an MHC-restricted T-B cell interaction. The present study was undertaken to investigate whether Th cells mediating a given immune response provide further regulatory function to B cells other than helper function. It was demonstrated that conditions of high antigen concentration which activate a noncognate B cell activation pathway simultaneously inhibit IgG responses. The inhibition is shown to be mediated by the T cell factor interleukin 4, produced by activated cloned Th cells. The inhibitory effect of this factor is directed to B cells and is MHC-unrestricted, antigen-nonspecific, and IgG class-specific. In addition to being susceptible to the effects of augmenting cells and suppressor cells, cloned Th cell populations can therefore themselves function as regulatory cells to inhibit IgG responses when stimulated with high dose of specific antigen. These results indicate that Th cells function to regulate B cells both positively and negatively, depending upon the activation conditions.

Animals↗
PubMed1987

The role of tumor-specific Lyt-1+2- T cells in eradicating tumor cells in vivo. II. Lyt-1+2- T cells have potential to reject antigenically irrelevant (bystander) tumor cells on activation with the specific target tumor cells.

The present study investigates some of mechanisms for tumor-specific Lyt-1+2- T cell-mediated tumor cell eradication in vivo through analyses of tumor specificity in the afferent tumor recognition and efferent rejection phases. When C3H/He mice which had acquired immunity against syngeneic MH134 hepatoma were challenged with other syngeneic X5563 plasmacytoma cells, these mice failed to exhibit any inhibitory effect on the growth of X5563 tumor cells. However, the inoculation of X5563 tumor cells into the MH134-immune C3H/He mice together with the MH134 tumor cells resulted in appreciable growth inhibition of antigenically distinct (bystander) X5563 tumor cells. Although the growth of X5563 cells was inhibited in an antigen-nonspecific way in mice immunized to antigenically unrelated tumor cells (bystander effect), the activation of Lyt-1+2- T cells leading to this effect was strictly antigen-specific. Such a bystander growth inhibition also required the admixed inoculation of the bystander (X5563) and specific target (MH134) tumor cells into a single site in mice immunized against the relevant MH134 tumor cells. Furthermore, the results demonstrated that Lyt-1+2- T cells specific to MH134 tumor cells were responsible for mediating the growth inhibition of antigenically irrelevant (bystander) and relevant tumor cells. These results are discussed in the context of cellular and molecular mechanisms involved in the Lyt-1+2- T cell-initiated bystander phenomenon.

Animals↗
PubMed2006

Curcumin (diferuloylmethane) inhibits constitutive active NF-kappaB, leading to suppression of cell growth of human T-cell leukemia virus type I-infected T-cell lines and primary adult T-cell leukemia cells.

Adult T-cell leukemia (ATL) is a fatal malignancy of T lymphocytes caused by infection with human T-cell leukemia virus type I (HTLV-I) and remains incurable. Curcumin (diferuloylmethane), the major pigment of the spice turmeric, can be potentially effective by promoting cell apoptosis. Here we examined whether curcumin is effective in the treatment of ATL. Curcumin prevented cell growth of HTLV-I-infected T-cell lines and primary ATL cells but not of normal peripheral blood mononuclear cells. Curcumin induced cell cycle arrest by reducing the expression of cyclin D1, Cdk1 and Cdc25C and apoptosis by reducing the expression of XIAP and survivin. Most of these genes are known to be regulated by NF-kappaB, which plays a critical role in oncogenesis by HTLV-I. Curcumin suppressed constitutive active NF-kappaB of HTLV-I-infected T-cell lines and primary ATL cells by inhibiting phosphorylation of IkappaBalpha. Curcumin also inhibited Tax-induced NF-kappaB transcriptional activity. However, curcumin-induced suppression of cell growth did not correlate with Tax expression level. Curcumin inhibited the growth of HTLV-I-infected T-cell tumors implanted subcutaneously in SCID mice. Our results indicate that curcumin has tumor-suppressive activity against ATL.

Adult↗
PubMed2006

Inhibition of constitutively active Jak-Stat pathway suppresses cell growth of human T-cell leukemia virus type 1-infected T-cell lines and primary adult T-cell leukemia cells.

BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1), the etiologic agent for adult T-cell leukemia (ATL), induces cytokine-independent proliferation of T-cells, associated with the acquisition of constitutive activation of Janus kinases (Jak) and signal transducers and activators of transcription (Stat) proteins. Our purposes in this study were to determine whether activation of Jak-Stat pathway is responsible for the proliferation and survival of ATL cells, and to explore mechanisms by which inhibition of Jak-Stat pathway kills ATL cells. RESULTS: Constitutive activation of Stat3 and Stat5 was observed in HTLV-1-infected T-cell lines and primary ATL cells, but not in HTLV-1-negative T-cell lines. Using AG490, a Jak-specific inhibitor, we demonstrated that the activation of Stat3 and Stat5 was mediated by the constitutive phosphorylation of Jak proteins. AG490 inhibited the growth of HTLV-1-infected T-cell lines and primary ATL cells by inducing G1 cell-cycle arrest mediated by altering the expression of cyclin D2, Cdk4, p53, p21, Pim-1 and c-Myc, and by apoptosis mediated by the reduced expression of c-IAP2, XIAP, survivin and Bcl-2. Importantly, AG490 did not inhibit the growth of normal peripheral blood mononuclear cells. CONCLUSION: Our results indicate that activation of Jak-Stat pathway is responsible for the proliferation and survival of ATL cells. Inhibition of this pathway may provide a new approach for the treatment of ATL.

Base Sequence↗
PubMed1993

Interaction of cutaneous stromal cells and gamma/delta T cell receptor (TcR)-positive cells. I. V gamma 5-gamma/delta TcR+ T cells migrating from organ-cultured murine skin proliferate by co-culture with cutaneous stromal cells in the presence of interleukin-2.

It has been reported that Thy-1+CD3+CD4-CD8- cells as well as Langerhans cells migrate from organ-cultured murine skin into culture medium. We examined whether these Thy-1+ populations of migrating cells were derived from Thy-1+ dendritic epidermal T cells (Thy-1+ DEC) and found that they were Thy-1+CD3+CD4-CD8-gamma/delta TcR+ (gamma delta+T) cells but did not express V gamma 5TcR, which was used by a vast majority of Thy-1+ DEC. Recently, a unique interaction between stromal cells and lymphohemopoietic progenitors has been reported in bone marrow and thymus. In this study, we established fibroblastoid cutaneous stromal cell (CSC) lines and clones from murine skin and examined the interaction between CSC and gamma delta+T cells. When these gamma delta+T cells were co-cultured with CSC, a marked proliferation of small lymphoid cells was observed only in the presence of interleukin (IL)-2. Neither CSC alone nor IL-2 alone could induce a similar proliferation. Flow cytometry revealed that they were Thy-1+CD3+CD4-CD8-gamma/delta TcR+ but V gamma 5TcR-. Analysis of the major segments of their TcR by polymerase chain reaction demonstrated that V gamma 1, V gamma 2, V gamma 4 and all of the V delta chains from V delta 1 to V delta 7 were used without any predominant pattern. These data indicate the possible presence of gamma/delta+T cells other than V gamma 5TcR+Thy-1+ DEC in the murine skin and the unique capacity of the CSC to support the growth of these migrating gamma/delta+ T cells. The nomenclature of murine T cell receptor gamma chain is according to Reilly et al. (Nature 1986. 321:878). The relationship between the different nomenclature systems is summarized in Takagi et al. (J. Immunol. 1989. 141:2112).

Animals↗
PubMed2004

Generation of cytotoxic donor CD8+ T cells against relapsing leukemic cells following allogeneic transplantation by stimulation with leukemic cell- or leukemic lysate pulsed donor cell-derived dendritic cells.

To treat leukemia relapse after allogeneic hematopoietic stem cell transplantation (HSCT), we investigated the possibility of immunotherapy using donor CD8+ T cells that were generated by stimulating leukemic cell-derived dendritic cells (leukemic-DCs) or leukemic cell lysate pulsed donor cell-derived DCs (donor-DCs). Leukemic- and donor-DCs were generated from mononuclear cells of patients and CD14+ cells of HLA-matched donors, respectively. The expression of CD80, CD83, CD86, CD1a, and CD40 on leukemic-DCs was significantly lower than that on donor-DCs. Donor-DCs exhibited a higher capacity to stimulate allogeneic T cells compared with leukemic-DCs. Donor CD8+ T cells stimulated by leukemic- or donor-DCs were more cytotoxic than unprimed CD8+ T cells, and slightly higher cytotoxicity was observed with donor-DCs compared to leukemic-DCs. This study indicates that leukemic- or donor-DCs pulsed with leukemic cell lysates can effectively prime donor cytotoxic T cells in vitro, and that they may be used as a potential alternative tool for treating leukemic patients who relapse after allogeneic HSCT.

CD8-Positive T-Lymphocytes↗
PubMed1993

Characterization of tumor necrosis factor alpha-induced alteration of glycosaminoglycans in cultured cells: comparison among vascular smooth-muscle cells, vascular endothelial cells, Chang liver cells and LLC-PK1 cells.

We investigated the alteration of glycosaminoglycans (GAGs) induced by recombinant human tumor necrosis factor alpha (rhTNF alpha) using confluent cultures of bovine aortic smooth-muscle cells, bovine aortic endothelial cells, Chang liver cells and porcine kidney LLC-PK1 cells. It was found that the incorporation of both [35S]sulfate and [3H]glucosamine into GAGs in the trypsinate fraction of the cell layer was significantly decreased by rhTNF alpha in vascular smooth-muscle cells and vascular endothelial cells; the incorporation of [35S]sulfate was increased but that of [3H]glucosamine was unchanged in Chang liver cells; the incorporation of both [35S]sulfate and [3H]glucosamine was increased by rhTNF alpha in LLC-PK1 cells. In the conditioned medium, the incorporation of both [35S]sulfate and [3H]glucosamine was not greatly changed by rhTNF alpha in all tested cell types. Characterization of GAGs revealed that each cell type uniquely altered its GAGs after rhTNF alpha treatment; the cytokine-induced alteration of each GAG component was not necessarily the same among different cell types. It was therefore concluded that rhTNF alpha-induced alteration of GAGs is dependent upon cell type.

Animals↗
PubMed1980

Cell-cell interactions in the T cell proliferative response. I. Analysis of the cell types involved and evidence for nonspecific T cell recruitment.

In the antigen-induced T cell proliferative response, it has been firmly established that antigen-specific T cell activation signals are provided by a specialized antigen-presenting cell (APC). However, the number of responding T cell populations involved has not been clearly delineated. This problem can be analyzed by plotting the logarithm of the number of cultured cells against the logarithm of the response. This yields a straight line, the slope of which indicates the minimum number of interacting cell populations that are required to give the response. In the antigen-induced T cell proliferative response, this number is 3. Based on their ability to shift the slopes of the log cell number-log response line, two of the populations were identified to be T cells. The third cell, which was present in irradiated spleens, possessed certain properties of the APC. Of the two T cells, one was antigen-specific and the other could come from normal unprimed animals. The frequency of antigen-specific proliferating T cells in primed animals was estimated to be only 1 in 1.3 x 10(3), and a large proportion of the proliferation was shown to be due to unprimed cells. Furthermore, without the need to use antigen-pulsed macrophages, this slope analysis demonstrated convincingly that the successful interaction between APCs and proliferating T lymphocytes is determined by products of the I-region immune response genes.

Animals↗
PubMed2000

Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells.

Cell death by necrosis is typically associated with inflammation, in contrast to apoptosis. We have identified additional distinctions between the two types of death that occur at the level of dendritic cells (DCs) and which influence the induction of immunity. DCs must undergo changes termed maturation to act as potent antigen-presenting cells. Here, we investigated whether exposure to apoptotic or necrotic cells affected DC maturation. We found that immature DCs efficiently phagocytose a variety of apoptotic and necrotic tumor cells. However, only exposure to the latter induces maturation. The mature DCs express high levels of the DC-restricted markers CD83 and lysosome-associated membrane glycoprotein (DC-LAMP) and the costimulatory molecules CD40 and CD86. Furthermore, they develop into powerful stimulators of both CD4(+) and CD8(+) T cells. Cross-presentation of antigens to CD8(+) T cells occurs after uptake of apoptotic cells. We demonstrate here that optimal cross-presentation of antigens from tumor cells requires two steps: phagocytosis of apoptotic cells by immature DCs, which provides antigenic peptides for major histocompatibility complex class I and class II presentation, and a maturation signal that is delivered by exposure to necrotic tumor cells, their supernatants, or standard maturation stimuli, e.g., monocyte-conditioned medium. Thus, DCs are able to distinguish two types of tumor cell death, with necrosis providing a control that is critical for the initiation of immunity.

Animals↗
PubMed1984

T cell regulation of B cell activation. An antigen-mediated tripartite interaction of Ts cells, Th cells, and B cells is required for suppression.

To determine the requirements underlying the antigen specificity observed in T cell-mediated immune response suppression, cloned major histocompatibility complex (MHC)-restricted T suppressor (Ts) cells specific for keyhole limpet hemocyanin (KLH) and cloned MHC-restricted T helper (Th) cells specific for fowl gamma-globulin (FGG) were employed to study the regulation of trinitrophenyl (TNP)-specific B cell responses. Neither antigen bridging between Ts cells and Th cells (FGG=KLH) nor bridging between Ts cells and B cells (TNP-KLH) was sufficient to allow suppression; a mixture of FGG=KLH and TNP-KLH was also insufficient for suppression. In contrast, suppression was induced by KLH-specific Ts cells only when suppressor determinants (KLH), helper determinants (FGG), and B cell determinants (TNP) were covalently linked on the same molecule (TMP-FGG)=(TNP-KLH) or TNP-(FGG=KLH)). These findings imply that a tripartite antigen-mediated interaction of Ts cells, Th cells, and responding B cells is necessary for the mediation of this antigen-specific suppression.

Animals↗
PubMed1999

Natural T cells in the human liver: cytotoxic lymphocytes with dual T cell and natural killer cell phenotype and function are phenotypically heterogenous and include Valpha24-JalphaQ and gammadelta T cell receptor bearing cells.

The adult liver contains lymphocytes with a unique phenotypic distribution compared to blood and other organs. We have characterized a human lymphocyte population that exhibits dual T cell and natural killer (NK) cell phenotype and function, denoted natural T (NT) cells, in nine normal adult liver specimens. Flow cytometry revealed that up to 55% (mean 27%) of hepatic (but <6% of peripheral) CD3+ lymphocytes expressed CD56, CD161 and/or one or more of the killer inhibitory receptors (KIR) p58.1, p58.2, p70 and CD94. NK function was attributed to the CD3+CD56+ cells by the demonstration that hepatic, but not peripheral, CD3+ lymphocytes could be induced to lyse NK-sensitive K562 target cells, while CD56- cells from both compartments could not. Three color flow cytometric analysis of fresh hepatic cells indicated that CD3+CD56+ NT cells can be either CD8+, CD4+ or CD4 CD8-, they express alphabeta or gammadelta T cell receptors (TCR) and CD161 and KIRs, but rarely CD16. Hepatic NT cells predominantly express the mature/activated CD45RO and CD56dim phenotypes. Analysis of mRNA production by isolated NT cells indicated a preferential usage of the invariant CD1-restricted Valpha24-JalphaQ TCR. The presence of such large numbers of chronically activated NT cells provides compelling evidence that the liver has unique immunoregulatory functions.

Adult↗