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At least 325 records · Page 18Linked to original sources
PubMed2003

Cholera toxin promotes the induction of regulatory T cells specific for bystander antigens by modulating dendritic cell activation.

It has previously been reported that cholera toxin (CT) is a potent mucosal adjuvant that enhances Th2 or mixed Th1/Th2 type responses to coadministered foreign Ag. Here we demonstrate that CT also promotes the generation of regulatory T (Tr) cells against bystander Ag. Parenteral immunization of mice with Ag in the presence of CT induced T cells that secreted high levels of IL-4 and IL-10 and lower levels of IL-5 and IFN-gamma. Ag-specific CD4(+) T cell lines and clones generated from these mice had cytokine profiles characteristic of Th2 or type 1 Tr cells, and these T cells suppressed IFN-gamma production by Th1 cells. Furthermore, adoptive transfer of bone marrow-derived dendritic cells (DC) incubated with Ag and CT induced T cells that secreted IL-4 and IL-10 and low concentrations of IL-5. It has previously been shown that IL-10 promotes the differentiation or expansion of type 1 Tr cells. Here we found that CT synergized with low doses of LPS to induce IL-10 production by immature DC. CT also enhanced the expression of CD80, CD86, and OX40 (CD134) on DC and induced the secretion of the chemokine, macrophage inflammatory protein-2 (MIP-2), but inhibited LPS-driven induction of CD40 and ICAM-I expression and production of the inflammatory cytokines/chemokines IL-12, TNF-alpha, MIP-1alpha, MIP-1beta, and monocyte chemoattractant protein-1. Our findings suggest that CT induces maturation of DC, but, by inducing IL-10, inhibiting IL-12, and selectively affecting surface marker expression, suppresses the generation of Th1 cells and promotes the induction of T cells with regulatory activity.

Adjuvants, Immunologic↗
PubMedDate not supplied

Infusion of anti-CD10 monoclonal antibody (J5) following ablative chemotherapy in a patient with refractory pre-B acute lymphoblastic leukemia.

The case of a 9-year old girl with end-stage refractory pre-B CD10/CALLA positive acute lymphoblastic leukaemia is described. The patient was treated with high doses of cytarabine followed by intravenous anti-CD10 monoclonal antibody (J5) in an effort to prevent the recovery of the leukemic CD10 positive clone following the bone marrow hypoplasia resulting from the chemotherapy. The number of CD10 positive cells dissapeared both in the peripheral blood as well as in the bone marrow, but when granulocytic recovery ensued, the patient died from respiratory infection. No evidence of antigenic modulation of the CD10 antigen was observed in the blast cells.

Antibodies, Monoclonal↗
PubMed1991

Modulation of antigen presentation and peptide-MHC-specific, LFA-1-dependent T cell-macrophage adhesion.

Incubation of peritoneal macrophages in vitro before fixation increased their ability to present exogenous peptides to 3A9 T hybridoma cells. The enhanced level of presentation correlated with a greatly increased, peptide-specific adhesion of 3A9 cells to the macrophages, whereas peptide-independent adhesion was minimal and essentially unaltered. 3A9 cells exhibited rapid peptide-specific adhesion (plateau by 5 to 10 min) and deadhesion (complete reversal by 5 min). Peptide-specific adhesion was blocked by anti-I-Ak and anti-LFA-1. Interaction of T cell receptors and CD-4 with peptide-I-Ak complexes appeared to provide little direct contribution to the avidity of T cell-macrophage adhesion, but activated a LFA-1-mediated adhesion mechanism. In addition, anti-T cell receptor, anti-CD3, and anti-CD4 antibodies themselves activated LFA-1-dependent adhesion in the absence of peptide. Unlike the peptide-induced adhesion, this adhesion was similar for macrophages whether or not they were incubated in vitro before fixation. We conclude that the different macrophage populations supported LFA-1-mediated adhesion equally. Therefore, the enhancement of T cell stimulation observed after in vitro incubation of macrophages was due to increased peptide presentation and consequently increased triggering of LFA-1-mediated adhesion. Mechanisms may exist to regulate the effectiveness with which peptide-class II MHC complexes are displayed for T cell recognition.

Animals↗
PubMed1988

Heritable high frequency modulation of antigen expression in neoplastic cells exposed to 5-aza-2'-deoxycytidine or hydroxyurea: analysis and implications.

A study was undertaken to determine the ability of the DNA hypomethylating drug 5-aza-2'-deoxycytidine (5-azadCyd) to induce antigen expression in a high proportion of treated tumor cells and to evaluate if this effect could be mimicked by the drug hydroxyurea (HU) which is a genomic DNA hypermethylating agent. Induction of heritable changes in gene expression by 5-azacytidine or the 2'-deoxy analogue (5-azadCyd), at least in some cases, may not be necessarily due to their hypomethylating properties, but to some other induced high frequency genetic change which occurs when DNA synthesis or repair is perturbed. A comparison of 5-azadCyd and HU effects on human and murine tumors was chosen for this study. The phenotypic properties examined with the above treatments were (a) induction of a Mr 110,000 antigen, detected with M111 antibody, in a variant subpopulation (SMeLus7) of human melanoma cells which fail to maximally express this antigen (M111). The parent cell line, MeWo, and other MeWo-derived variant cell cell lines do not demonstrate a similarly inducible phenotype; and (b) induction of class I major histocompatibility complex antigens in a population of mouse mammary adenocarcinoma cells which normally fail to express these antigens. The results showed that 5-azadCyd was effective in inducing antigen expression in both systems whereas HU was effective (and equally so) only in the human melanoma cell line system. In these treatments 5-azadCyd was demonstrated to transiently hypomethylate the same human melanoma cell line whereas HU hypermethylated genomic cytosines. The results suggest that some of the reported effects of 5-azacytidine or 5-azadCyd in inducing very high frequency heritable phenotypic alterations may not necessarily be related to the drugs' ability to cause DNA hypomethylation. The implications of these results are discussed in terms of the use of 5-azacytidine or 5-azadCyd and the effects of chemotherapy on tumor progression and metastasis.

Animals↗
PubMed1989

Regulation of MHC expression in vivo. II. IFN-alpha/beta inducers and recombinant IFN-alpha modulate MHC antigen expression in mouse tissues.

We examined the effect of type I IFN inducers and rIFN-alpha on MHC expression in mouse tissues in vivo. MHC expression was assessed in a radiolabeled mAb binding assay and by indirect immunoperoxidase staining of tissue sections. polyI:C, an inducer of IFN-alpha/beta, induced large increases in class I MHC in many tissues, with little effect on class II expression. In the kidney, which was studied in detail, polyI:C increased class I expression from day 1 to day 6, localized in glomeruli, tubules, and arterial endothelium. Renal class II MHC was less affected but tended to be decreased at days 3 to 6, corresponding to diminished staining of class II-positive interstitial cells. polyI:C increased renal class I MHC in nude mice and mice with severe combined immunodeficiency, and in mice treated with cyclosporine or mAb against IFN-gamma. The effects of influenza virus resembled those of polyI:C. However, a potent T cell stimulus, allogeneic ascites tumor cells, induced markedly different MHC changes, with massive and sustained increases in class I and II, presumably due to IFN-gamma release, which was inhibited by cyclosporine or by mAb against IFN-gamma. The effect of polyI:C was largely simulated by rIFN-alpha, whereas the effect of allogeneic cells was simulated by rIFN-gamma. Thus, rIFN-alpha and its inducers in vivo produce a sustained increase in renal class I expression in kidney and other tissues, sometimes with changes in class II expression. Such effects could be relevant to the immune modulatory actions of IFN, and to the immunologic consequences of viral infections.

Adjuvants, Immunologic↗
PubMed1987

Mechanisms of benzo(a)pyrene-induced modulation of antigen presentation.

Benzo(a)pyrene (BaP) has been shown previously to affect humoral immunity in part through alterations in the normal functioning of macrophages. In this study we investigated several specific events affected by BaP. Concanavalin A-elicited macrophages from BaP-exposed animals had a decreased capacity to present keyhole limpet hemocyanin (KLH) to nylon wool nonadherent, KLH-primed lymph node T cells. BaP treatment 7 days before and after administration of KLH resulted in a decrease in the responsiveness of KLH primed T cells to antigen. BaP administration beginning 3 days before (day -3), concurrently with (day 0) or 7 days after (day +7) KLH antigen treatment had no effect on the ability of KLH primed T cells to respond to KLH presented by untreated macrophages. The decreased capacity of BaP-exposed macrophages to present KLH is due in part to a decrease in the amount of KLH taken up by these cells. There was no alteration in the amount of soluble interleukin-1 released by BaP exposed cells or was there a change in the expression of membrane associated interleukin-1. BaP treatment resulted in a dose-dependent increase in the percentage of Ia+ macrophages. These results demonstrate that BaP affects antigen presentation through alteration in macrophage function.

Animals↗
PubMed1995

Isotype-associated recognition of allergen epitopes and its modulation by antigen dose.

The existence of competing and blocking IgG antibodies and their interrelationship with IgE antibodies was investigated in the IgE immune response of CBA/J mice to bee venom phospholipase A2 (PLA2) and keyhole limpet haemocyanin (KLH). Minute doses of antigen induced high titres of both IgE and IgG antibodies, whereas large doses elicited high IgG responses but only weak IgE antibody titres. Immunization with minute doses of antigen led to the production of antibodies with class-associated epitope specificities (designated epitopes G for IgG and E for IgE antibodies), and therefore no competition was observed. For IgG antibody production, G epitopes were immunodominant and IgG antibodies directed to E epitopes were produced only after immunization with an increased immunogen dose. Under this condition IgG antibodies recognizing the E epitopes acted as blocking antibodies competing with IgE antibodies for binding to E epitopes, the immunodominant epitopes for the IgE response. The data demonstrate the existance of distinct immunodominant antigenic determinants for IgE and IgG antibodies on PLA2.

Animals↗
PubMed1996

Modulation of antigen presentation and class II expression by a class II-associated invariant chain peptide.

During the process of MHC class II assembly, the class II-associated invariant chain peptide (CLIP) remains bound within the peptide binding groove until its subsequent removal, which is mediated by H-2 M. We have defined the functional role of CLIP, through saturation of the endosomal compartment with exogenous CLIP-(85-101), resulting in reduced class II MHC on the surface of APCs and an impeded T cell response. Conversely, incubation of the same cells with immunogenic peptides or proteins resulted in an up-regulation of surface class II MHC. T cells from CLIP- plus Ag-immunized mice showed a marked decrease in Ag-specific response over that in mice primed with Ag alone. A B cell hybridoma, TA3 (H-2d,k) incubated with CLIP in vitro showed dramatically reduced MHC class II I-A surface expression. APCs derived from CLIP-immunized mice exhibited down-regulation of surface class II MHC, but not of CD45 (B220). Electrophoretic studies showed that the addition of exogenous CLIP resulted in a relative decrease in SDS-stable MHC class II heterodimers in TA3 cells. Studies with FITC-CLIP and FITC-OVA-(323-339) peptides demonstrated that exogenously added CLIP peptide does not bind to surface class II molecules via the endogenous route, whereas OVA peptide does. This suggests that exogenously added CLIP acts intracellularly, perhaps in the compartment where H-2 M intersects with class II molecules. These findings demonstrate the functional role of CLIP to regulate MHC class II-mediated Ag presentation in CD4+ T cell responses.

Amino Acid Sequence↗
PubMed1991

A novel surface molecule expressed by long-term cultured T and natural killer cells is involved in cell activation.

Two monoclonal antibodies (mAb), termed ED6 and LD6, were obtained by immunizing mice with cytotoxic T cell lines expressing the T cell receptor (TcR) gamma/delta. These mAb were selected according to their ability to trigger the cytolytic program of the immunizing cell lines in a redirected killing assay. Both mAb recognized molecule(s) expressed on the surface of most long-term cultured TcR gamma/delta +, TcR alpha/beta + and CD3-CD16+ lymphocytes, while it was absent on resting peripheral blood lymphocytes. In addition both mAb reacted with neoplastic B cell lines, Epstein-Barr virus-transformed B cell lines, small cell lung cancer and glioma cell lines, while no surface reactivity was detected on ovarian, breast, colon and non-small cell lung cancer lines. The functional activity of these mAb was studied by two cytolytic assays. Both mAb were able to trigger the cytolytic program of CD3+TcR gamma/delta + polyclonal cell lines and of a CD3-CD16+ NK cell clone against the murine mastocytoma target cell line P815 (Fc receptor+) in a 4-h 51Cr-release assay. In addition, ED6 and LD6 hybridomas were lysed by TcR gamma/delta + effector cells while other hybridomas (obtained from the same fusion) were not lysed. ED6 and LD6 mAb (in the presence of submitogenic doses of the phorbol 12-myristate 13-acetate) also induced the secretion of interleukin 2 by ED6/LD6+ T cell clones expressing TcR gamma/delta or alpha/beta. mAb-induced surface antigen modulation experiments showed that the antigenic determinant recognized by ED6 and LD6 co-modulated, thus indicating that the two mAb probably recognize the same or closely associated molecules. The molecular characteristics of the antigen recognized by the mAb were investigated by Western blot analysis. The LD6 mAb recognized a major band of approximately 65 kDa, both under nonreducing and reducing conditions. These data indicate that ED6 and LD6 mAb recognize a novel non-lineage-specific activation antigen which is involved in the induction of the functional program of long-term cultured T or natural killer cells.

Animals↗
PubMed1992

Modulation of the antigenic phenotype of human breast carcinoma cells by modifiers of protein kinase C activity and recombinant human interferons.

In the present study we have analyzed the effect of a synthetic protein kinase C (PKC) activator 3-(N-acetylamino)-5-(N-decyl-N-methylamino)-benzyl alcohol (ADMB) and the natural PKC-activating tumor-promoting agents 12-O-tetradecanoylphorbol 13-acetate (TPA) and mezerein on the antigenic phenotype of T47D human breast carcinoma cells. All three agents increased the surface expression of the tumor-associated antigen BCA 225 and various cellular antigens, including HLA class II antigens, intercellular adhesion molecule 1 (ICAM-1) and c-erbB-2. Expression of the same antigens was also upregulated to various extents in T47D cells by recombinant fibroblast (IFN beta) and immune (IFN gamma) interferon. Shedding of BCA 225 from T47D cells was induced by TPA, mezerein, IFN beta and IFN gamma, whereas ADMB did not display this activity. The ability of ADMB, TPA and mezerein to modulate the antigenic phenotype of T47D cells appears to involve a PKC-mediated pathway, since the PKC inhibitor, H-7, eliminates antigenic modulation. In contrast, the ability of IFN beta and IFN gamma to enhance the synthesis, expression and shedding of BCA 225, as well as to enhance HLA class II antigens, c-erbB-2 and ICAM-1 expression, was either unchanged or modestly reduced by simultaneous exposure to H-7. Analysis of steady-state mRNA levels for HLA class I antigens, HLA class II-DR beta antigen, ICAM-1 and c-erbB-2 indicated that the ability of H-7 to inhibit expression of these antigens in TPA-, mezerein- and ADMB-treated cells was not a consequence of a reduction in the steady-state levels of mRNAs for these antigens. The results of the present investigation indicate that the biochemical pathways mediating enhanced antigenic expression in T47D cells induced by TPA, mezerein and the synthetic PKC activator ADMB are different from those induced by recombinant interferons. Furthermore, up-regulation of antigenic expression in T47D cells can occur by a PKC-dependent or a PKC-independent pathway.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1988

Decreased expression of CD7 occurs in rheumatoid arthritis.

To evaluate the possibility of antigenic modulation in vivo, we studied the expression of the CD7 antigen on the surface of peripheral blood and intrasynovial lymphocytes from patients with rheumatoid arthritis (RA). This disease is noted for features predicting changes in CD7: (1) increased expression related to activation during an immune response through possible contact with 'disease associated antigens' and (2) decreased expression associated with lymphocytes moving through tissue. We found a highly significant decrease of CD7 on RA T cells in vivo (P less than 10(-4] that was not related to disease activity, drug ingestion, or abnormalities in the ability of RA T cells to express or modulate the antigen in vitro. Similar decreased expression was observed on many intrasynovial T cells that were nevertheless activated as measured by expression of activation markers such as Act I (a late lymphocyte activation antigen) and Act II (the transferrin receptor). Decreased expression of CD7 occurs naturally in vivo in RA; this observation may have future significance in better understanding the immunopathogenesis of this disease.

Adult↗
PubMed1987

Modulation of CD4 antigen expression on human gingival Langerhans cells by gamma interferon.

Human gingival organ culture was used to test the hypothesis that gamma interferon (gamma-IFN), which induces HLA-DR and HLA-DQ antigens on Langerhans cells, modulates CD4 antigen expression on these same cells. Before culture, the density of CD4+ cells in the gingival epithelium was 12.7% +/- 3.8% of the density of CD1+ cells. gamma-IFN (200 IU/ml) enhanced CD4 expression such that at 24 h, all CD1+ cells also expressed CD4. Prostaglandin E2, which in isolation had no effect, partially abrogated the stimulatory effect of gamma-IFN on CD4 expression. These results imply that gamma-IFN and prostaglandin E2 are two signals which regulate CD4 expression on gingival Langerhans cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Lymphocytes modulated by beta interferon express new non-HLA-A,B,C class I antigens.

Peripheral blood lymphocytes were cultured with recombinant beta interferon (INF-lymph). Three days in culture and 5 X 10(4) units/ml produced the best modulatory effect. Platelet absorbed alloantisera previously shown to contain non-HLA-A,B,C class I antibodies were tested with the INF-lymph. The serologic reactivity could be blocked by turkey sera to human B2-microglobulin but not by turkey anti-Ia-like. Absorption studies with INF-lymph obtained from donors expressing different HLA antigens indicated that the serologic reactivity is not due to HLA. Fourteen sera appeared to cluster in three groups, only one of which was found to be associated with HLA (HLA-A1). Antigenic modulation of INF-lymph obtained from HLA-A1+ individuals with HLA-A1 typing alloantisera eliminated subsequent lysis mediated by HLA-A1 alloantibodies and complement but not lysis with platelet absorbed antibodies included in the cluster associated with HLA-A1. These findings suggest independence from HLA-A1 and coexpression of HLA-A1 and A1-associated class I antigens. Family studies indicated that the reactivities segregated with HLA thus mapping it to chromosome VI. Similar to what we have described with PHA, beta interferon modulates lymphocytes and induces the expression of new class I differentiation antigens probably analogous to the murine Qa-T1a antigens.

Blood Platelets↗
PubMed2006

Monoclonal antibody therapy for hairy cell leukemia.

The use of MoAb therapy for the treatment of HCL offers great promise and potential for improving progression-free survival. Rituximab has activity in the setting of previously treated HCL and the ability to eradicate MRD after 2-CdA given as frontline therapy. Alemtuzumab, epratuzumab, Hu-Max-CD20, and other candidate MoAb's should be studied in HCL. Appropriate pharmacologic investigation, use of antigen modulation, and assessments of soluble antigen levels should be considered with future clinical trial s of MoAb's in HCL to optimize therapeutic strategies.

Antibodies, Monoclonal↗
PubMed1972

Mouse thymus-independent and thymus-derived lymphoid cells. I. Immunofluorescent and functional studies.

The simultaneous use on mouse lymphoid suspensions of heterologous antisera directed against thymus-derived (T) cell mouse-specific lymphocyte antigen and brain-associated theta antigen (MSLA and BAtheta) or thymus-independent (B) cell mouse-specific bone marrow-derived lymphocyte antigen (MBLA) surface antigens allowed direct proof of the different specificity of these antisera by double immunofluorescence (IF) staining with selective visualization of fluorochromes. These antisera and antisera against mouse Ig and its different types of chains were then used with technique of either double IF staining or IF combined with radioautography, allowing the following conclusions: (a) Surface Ig (sIg) was found exclusively on B cells and never on T cells, but not all B cells had sIg. Cells containing detectable amounts of Ig were MBLA+, but had less sIg than other B cells or none at all. There was evidence for the existence of a significant number of MBLA+ lymphocytes, neither bearing nor containing detectable Ig. (b) micro-Chains were the most frequent but not the only heavy chains found on spleen cells; however, it could not be decided with the technique used, if a single cell can bear more than one type of heavy chain. No cell containing gamma-chains was found to bear surface micro-chains, although a very few cells containing both micro- and gamma-chains were observed. (c) The antigen-binding cells detected after immunization with bacteriophage T4, bovine serum albumin, Maia squinado hemocyanin, and sheep erythrocytes were analyzed for MSLA, MBLA or sIg using double IF, a combination of IF and radioautography, or inhibition of "rosette" formation. Practically all the antigen-binding cells detected were MSLA-, MBLA+, sIg+. (d) More B cells than T cells were found among short-lived lymphoid cells labeled by repeated in vivo injections of tritiated thymidine, but the results did not support a simplified concept equating T cells to long-lived and B cells to short-lived lymphocytes. (e) Cells dividing rapidly in the lymph nodes draining the sites of immunization with various antigens were predominantly T cells 2 days after immunization and in majority B cells a few days later. (f) Incubation of lymphoid cells at 37 degrees C with rabbit anti-mouse Ig or anti-kappa chains led to complete disappearance of sIg and to decrease of MBLA ("antigenic modulation"). In the same conditions, anti-MBLA gave partial modulation of MBLA and of sIg; MBLA, however, reappeared much faster than sIg. No modulation of T cell surface antigens by the appropriate antisera was observed. Cell treatment with Pronase could remove MBLA, sIg, MSLA, and BAtheta, which reappeared within a few hours. Neuraminidase treatment was without detectable effect on these antigens.

Animals↗