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Results for “Antigenic Modulation”

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PubMed2003

Transforming growth factor-beta inhibits human antigen-specific CD4+ T cell proliferation without modulating the cytokine response.

Transforming growth factor (TGF)-beta has been demonstrated to play a key role in the regulation of the immune response, mainly by its suppressive function towards cells of the immune system. In humans, the effect of TGF-beta on antigen-specific established memory T cells has not been investigated yet. In this study antigen-specific CD4(+) T cell clones (TCC) were used to determine the effect of TGF-beta on antigen-specific proliferation, the activation status of the T cells and their cytokine production. This study demonstrates that TGF-beta is an adequate suppressor of antigen-specific T cell proliferation, by reducing the cell-cycle rate rather than induction of apoptosis. Addition of TGF-beta resulted in increased CD69 expression and decreased CD25 expression on T cells, indicating that TGF-beta is able to modulate the activation status of in vivo differentiated T cells. On the contrary, the antigen-specific cytokine production was not affected by TGF-beta. Although TGF-beta was suppressive towards the majority of the T cells, insensitivity of a few TCC towards TGF-beta was also observed. This could not be correlated to differential expression of TGF-beta signaling molecules such as Smad3, Smad7, SARA (Smad anchor for receptor activation) and Hgs (hepatocyte growth factor-regulated tyrosine kinase substrate). In summary, TGF-beta has a pronounced inhibitory effect on antigen-specific T cell proliferation without modulating their cytokine production.

Animals↗
PubMed1985

Immunochemical analysis of the modulation of human melanoma-associated antigens by DNA recombinant immune interferon.

By utilizing the human melanoma cell line Colo 38, a panel of monoclonal antibodies, and a combination of serologic and immunochemical assays, the effect of recombinant immune interferon (IFN-gamma) on the synthesis, expression, and shedding of a cytoplasmic melanoma-associated antigen (MAA) and of the membrane-bound high m.w. MAA (HMW-MAA), 115K MAA, and 100K MAA has been investigated. IFN-gamma increased the synthesis and shedding of the cytoplasmic MAA, but reduced the synthesis and cell surface expression of the HMW-MAA and of the 100K MAA. The cell surface expression of the 115K MAA on IFN-gamma-treated melanoma cells was reduced, although its synthesis was not markedly changed. The effects were dose-dependent and were related to the incubation time of cells with IFN-gamma. Among the three membrane-bound MAA analyzed, the 100K MAA was the most susceptible to modulation by IFN-gamma. The effects of IFN-gamma preparations are not mediated by contaminants in IFN-gamma preparations because removal of IFN-gamma by affinity chromatography on anti-IFN-gamma monoclonal antibodies abolished its modulating activity. The effects of IFN-gamma on the cytoplasmic MAA are similar to those of leukocyte and fibroblast interferons, whereas those on the membrane-bound MAA are significantly different. The potential implications of the marked changes in the antigenic profile of melanoma cells treated with IFN-gamma are discussed in view of the changes in the immunogenicity of IFN-gamma-treated melanoma cells.

Animals↗
PubMed1982

Human mononuclear phagocytes differentiation antigens.

Cell surface antigenic analysis using 10 different monoclonal antibodies indicates the following. (a) The membrane antigenic phenotype of various members of the mononuclear phagocyte lineage is characterized by the co-expression of multiple but distinct antigenic determinants. (b) The maturational evolution of the cells is associated with qualitative and/or quantitative modifications of cell surface antigens resulting in the definition of different phenotypic entities. (c) In vitro culture of blood monocytes is accompanied by significant modulation of these antigens. In particular, the expression of MoP-15 appears to be modulated following in vitro activation. (d) The occurrence of these antigens on various normal and leukemic cell populations provides a basis for the establishment of defined patterns of antigenic expression corresponding to successive maturational states of the human mononuclear phagocyte cell lineage. (e) The reactivity of AML cells with various antibodies defines patterns of antigen expression related to the degree of leukemic cell maturity. These patterns change during culture.

Acute Disease↗
PubMed1992

Simian virus 40 T antigen activates the late promoter by modulating the activity of negative regulatory elements.

Late promoter activity measured before viral DNA replication results from a complex involvement of negative and positive cis-acting elements located both in the enhancer and in the 21-bp repeats. GC motifs located within the 21-bp repeats act in cooperation with sequences overlapping the early TATA box to down-regulate the late promoter activity. Analysis of insertion mutants indicates that the late promoter might be negatively regulated at least partially by the early promoter machinery. The GTI motif located within the enhancer as well as the GC motifs lose the ability to down-regulate the late promoter in the presence of T antigen. Results obtained with tsA58 protein indicate that two different domains of T antigen are involved in the negative autoregulation of the early promoter activity and in the release of the down-regulation of the late promoter by the GC motifs.

Animals↗
PubMed2003

Presentation of donor major histocompatibility complex antigens by bone marrow dendritic cell-derived exosomes modulates allograft rejection.

BACKGROUND: Dendritic cells secrete a population of "antigen-presenting vesicles," called exosomes, expressing functional class I and II major histocompatibility complex (MHC) and co-stimulatory molecules. The subcutaneous administration of syngeneic exosomes expressing tumor antigens has been shown to induce specific antitumor immune responses in vivo. The authors hypothesized that antigen presentation by exosomes, depending on the context of their administration, may induce tolerance rather than immunity. METHODS: The authors therefore tested the capacity of exosomes derived from donor bone marrow dendritic cells, given before transplantation, to modulate heart allograft rejection. RESULTS: The authors show here that donor type but not syngeneic exosomes induced a significant prolongation of allograft survival, with a few recipients having long-term graft survival. During the first week after transplantation, allografts from exosome-treated rats displayed a significant decrease in graft-infiltrating leukocytes and in the expression of interferon-gamma mRNA compared with allografts from untreated animals. Moreover, when tested in vitro, spleen CD4+ T cells from exosome-treated recipients displayed a significant decrease in anti-donor responses, suggesting a decrease in anti-donor T-cell responses. However, the authors also found that allogeneic donor-derived exosomes increased anti-donor MHC class II alloantibody production. CONCLUSIONS: The authors demonstrate an effect of allogeneic exosomes on the modulation of immune responses in vivo, suggesting that, like donor cells, exosomes can stimulate or regulate antigen-specific immune responses.

Animals↗
PubMed2006

Biosignals modulated by tumor-associated carbohydrate antigens: novel targets for cancer therapy.

Based on the remodeling of glycosphingolipids on the human tumor cell lines with manipulation of glycosyltransferase genes, roles of sugar moieties in tumor-associated carbohydrate antigens have been analyzed. Two main topics, that is, the roles of ganglioside GD3 in human malignant melanomas and those of GD2 in small cell lung cancer (SCLC) were reported. GD3 enhances tyrosine phosphorylation of two adaptor molecules, p130Cas and paxillin, resulting in the increased cell growth and invasion in melanoma cells. GD2 also enhances the proliferation and invasion of SCLC cells. GD2 also mediates apoptosis with anti-GD2 monoclonal antibodies (mAbs) via dephosphorylation of the focal adhesion kinase. These approaches have promoted further understanding of mechanisms by which gangliosides modulate malignant properties of human cancer, and the results obtained here propose novel targets for cancer therapy.

Anoikis↗
PubMed2006

Schistosoma japonicum egg antigens stimulate CD4 CD25 T cells and modulate airway inflammation in a murine model of asthma.

A number of epidemiological and clinical studies have suggested an inverse association between allergy and helminth infection, such as Schistosomiasis. Therefore, we hypothesize that Schistosoma japonicum egg antigens, a type of native antigen, can induce production of CD4(+) CD25(+) T cells with regulatory activity, modulating airway inflammation and inhibiting asthma development. The frequency of CD4(+) CD25(+) T cells was determined by flow cytometry for mice treated with ovalbumin (OVA), CD25(+) depletion/OVA, schistosome egg antigens, schistosome egg antigens/OVA and for control mice. The ability of CD25(+) T cells from these mice to suppress T-cell proliferation and cytokine production was investigated both in vivo and in vitro. Results showed that the CD4(+) CD25(+) T cells of OVA-treated mice exhibited impaired control of dysregulated mucosal T helper 2 responses compared to the controls (P < 0.05). Depletion of CD25(+) cells accelerated OVA-induced airway inflammation and increased the expression of interleukin (IL)-5 and IL-4. Treatment with schistosome egg antigens increased the number and suppressive activity of CD4(+) CD25(+) T cells, which made IL-10, but little IL-4. In a murine model of asthma, S. japonicum egg antigens decreased the expression of Th2 cytokines, relieved antigen-induced airway inflammation, and inhibited asthma development. Thus, we provided evidence that S. japonicum egg antigens induced the production of CD4(+) CD25(+) T cells, resulting in constitutive immunosuppressive activity and inhibition of asthma development. These results reveal a novel form of protection against asthma and suggest a mechanistic explanation for the protective effect of helminth infection on the development of allergy.

Animals↗
PubMed1978

Antibody response to a polysaccharide antigen present in the schistosome gut. II. Modulation of antibody response.

Specific IgM and IgG antibody to a polysaccharide present in the epithelial cells of the gut of adult schistosomes was measured in four groups of infected patients: I) patients with documented acute schistosomiasis; II) Americans exposed to schistosomiasis within the preceding 0--4 years; III) chronically and heavily infected patients, mostly from Puerto Rico, without hepatomegaly or hepatosplenomegaly; and IV) heavily infected Brazilian children with hepatic or hepatosplenic schistosomiasis. Specific IgM and IgG titers were both highest in the acute Group I patients and lowest in the chronically infected Groups III and IV. Total IgG and IgM levels were compared to specific antibody titers. Immunoglobulin levels tended to follow specific antibody titers except in the chronically infected Groups III and IV in which total IgG rose to high levels. The decrease in specific antigen titers over the course of time occurred despite continued antigenic stimulation and suggests a modulation of the humoral response. The mechanism remains obscure.

Adult↗
PubMed1990

Recombinant human interferon gamma exerts an anti-proliferative effect and modulates the expression of human leukocyte antigens A,B,C and DR in human urothelial cell lines.

In this study we have treated three malignant (TGrIII) and two pre-malignant (TGrII) urothelial cell lines with recombinant human interferon gamma (rHu-INF gamma). The malignant cells (HCV29-T112C1, Hu1703He and T24) were inhibited in growth by more than 50% after treatment with 100-1000 units of rHu-INF gamma/ml for 4 days as compared to untreated controls. The growth of the pre-malignant cell lines (HCV29 and Hu609) was not influenced to the same extent in the presence of rHu-INF gamma in the culture medium. Treatment with rHu-INF gamma increased the expression of monomorphic human leukocyte antigens (HLA) A,B,C as well as beta 2-microglobulin in all the cell lines tested, as demonstrated using a quantitative immunofluorescence assay. The tumourigenic cell lines increased their expression of HLA in a dose-dependent way, whereas treatment of the non-tumourigenic cells with higher concentrations of rHu-INF gamma than 10 units/ml, did not increase the HLA-A,B,C expression further. None of the cell lines expressed HLA-DR unless treated with rHu-INF gamma. No correlation between tumourigenicity and the dose of rHu-INF gamma required for "de novo" induction of HLA-DR could be demonstrated. After removal of rHu-INF gamma from the medium, the expression of HLA-DR gradually decreased in less than 14 days, indicating that the expression of HLA-DR is not constitutive but dependent upon the presence of rHu-INF gamma. We conclude that human urothelial cells grown in vitro are sensitive to the anti-proliferative and major-histocompatibility-complex-modulating effects of rHu-INF gamma, and that malignant urothelial cells are more sensitive than pre-malignant cells. Finally, our data indicate a possible role for rHu-INF gamma in the management of human bladder cancer.

Animals↗
PubMed2004

Cross-regulation of CD86 by CD80 differentially regulates T helper responses from Mycobacterium tuberculosis secretory antigen-activated dendritic cell subsets.

We report that stimulation of Mycobacterium tuberculosis secretory antigen- and tumor necrosis factor alpha-matured BALB/c mouse bone marrow dendritic cells (BMDCs) with anti-CD80 monoclonal antibody up-regulated CD86 levels on the cell surface. Coculture of these BMDCs with naïve, allogeneic T cells now down-regulated T helper cell type 1 (Th1) responses and up-regulated suppressor responses. Similar results were obtained with splenic CD11c(+)/CD8a(-) DCs but not to the same extent with CD11c(+)/CD8a(+) DCs. Following coculture with T cells, only BMDCs and CD11c(+)/CD8a(-) DCs and not CD11c(+)/CD8a(+) DCs displayed increased levels of surface CD86, and further, coculturing these DCs with a fresh set of T cells attenuated Th1 responses and increased suppressor responses. Not only naïve but even antigen-specific recall responses of the Th1-committed cells were modulated by DCs expressing up-regulated surface CD86. Further analyses showed that stimulation with anti-CD80 increased interleukin (IL)-10 and transforming growth factor-beta-1 levels with a concomitant reduction in IL-12p40 and interferon-gamma levels from BMDCs and CD11c(+)/CD8a(-) DCs and to a lesser extent, from CD11c(+)/CD8a(+) DCs. These results suggest that cross-talk between costimulatory molecules differentially regulates their relative surface densities leading to modulation of Th responses initiated from some DC subsets, and Th1-committed DCs such as CD11c(+)/CD8a(+) DCs may not allow for such modulation. Cognate antigen-presenting cell (APC):T cell interactions then impart a level of polarization on APCs mediated via cross-regulation of costimulatory molecules, which govern the nature of subsequent Th responses.

Animals↗
PubMed2002

The expression of T-cell surface antigens CTLA-4, CD26, and CD28 is modulated by inhibition of dipeptidylpeptidase IV (DPP IV, CD26) activity in murine stress-induced abortions.

Inhibition of DPP IV has been shown to abrogate the stress-related increase in murine abortions and a concomitant increase in gamma-interferon. The aim of the present study was to investigate a potential impact of the DPP IV inhibitor Isoleucine Cyanopyrrolidide on the expression of surface antigens involved in T-cell responses. DBA/2-mated CBA mice were stressed on day 5.5 of pregnancy and received injections of a DPP IV inhibitor. On day 13 of gestation, the animals were sacrificed and the percentage of abortions was determined. As shown before, stress failed to boost the abortion rate in mice receiving the DPP IV inhibitor. In stressed animals, a lower surface density of CTLA-4 on decidual CD26-positive lymphocytes was observed than in non-stressed animals. Inhibition of DPP IV restored CTLA-4 surface density to normal and decreased surface expression of CD26 and CD28 on decidual lymphocytes irrespective of stress exposure. These observations suggest that a modulation of T-cell surface antigens expression due to inhibition of DPP IV activity may contribute to the potent anti-abortogenic effect observed here.

Abatacept↗
PubMedDate not supplied

Receptor isoform and ligand-specific modulation of dihydrotestosterone-induced prostate specific antigen gene expression and prostate tumor cell growth by estrogens.

Androgens via the androgen receptor (AR) play crucial roles in prostate physiology and pathophysiology. These androgen actions can be either inhibited or potentiated by estrogens. The mechanisms of these seemingly opposing estrogen effects are unclear. We studied the effects of estrogens on the modulation of androgen induction of prostate specific antigen (PSA) gene expression and prostate tumor cell growth. Cotransfection analyses in CV-1, DU-145, and PC-3 cells showed that dihydrotestosterone (DHT)-induced PSA transcription activity was inhibited by 17beta-estradiol, diethylstilbestrol, ICI182780, and 17alpha-estradiol, but not by tamoxifen via estrogen receptor alpha (ERalpha). In the presence of ERbeta, 17beta-estradiol and diethylstilbestrol had no significant effect, while 17alpha-estradiol inhibited and ICI182780 and tamoxifen potentiated DHT action. When both ERalpha and ERbeta were present, all ER-ligands except tamoxifen inhibited DHT action. The inhibition of DHT action by 17beta-estradiol via ERalpha was mainly dependent on the DNA binding domain, while the 17alpha-estradiol effect was mainly dependent on the ERalpha carboxyl terminus. Treatment with DHT in LAPC-4 prostate tumor cells that express a wild-type AR and both ERbeta and ERalpha greatly increased the PSA gene expression and cell growth. These DHT effects were significantly attenuated by the addition of 17alpha-estradiol, 17beta-estradiol, or cyproterone acetate in a dose-dependent manner. These results indicate that estrogens produce an ER-isoform- and ER-ligand-specific modulation of DHT induction of PSA gene expression and prostate tumor cell growth, providing a molecular basis for designing favorable agents for the prevention and control of prostate cancer.

Animals↗
PubMed1994

Antigen-specific early primary humoral responses modulate immunodominance of B cell epitopes.

Accumulation of primary Abs against two distinct epitopes on a designed polypeptide, MEP-1, was examined. The early primary response was predominantly against a C-terminal epitope (MEP 77-100), although subsequent maturation established an epitope within the N-terminal half (MEP 17-31) as the immunodominant one. Inversion of immunodominance correlated with the inability of anti-MEP 77-100 B cells to interact productively with T cells, which consequently received reduced help. Interaction between epitope-specific B and T cells was found to be attenuated in the presence of early primary anti-MEP-1 antiserum, and the extent of inhibition was directly proportional to the level and affinity of epitope-specific Igs. Therefore, it seems that early primary Abs to a multideterminant Ag selectively down-regulate maturation of epitope-specific primary humoral responses.

Amino Acid Sequence↗
PubMed1995

Structural polymorphism and function of HLA-B27.

Over the past year, new subtypes have been described and significant advances have been made in understanding peptide binding to HLA-B27. These developments help in interpreting how antigen presentation is modulated by HLA-B27 polymorphism, in determining the similarities and differences in T cell antigenicity among subtypes, and in finding the basis of HLA-B27 evolution. New insights into the pathogenetic link between enteric bacteria and HLA-B27 come from demonstration of a direct relationship between gut flora and joint inflammation in transgenic rats and from involvement of HLA-B27 in modulating bacterial invasion of mammalian cells. The association between HLA-B27 and spondyloarthropathy may be related to antigen-presenting specificity, but a different mechanism, presentation of a B27-derived peptide by class II antigens, may contribute to the pathogenesis of acute anterior uveitis, emphasizing the need for a comprehensive understanding of the structure, antigenicity, and function of HLA-B27.

Animals↗
PubMed1994

Modulation of the expression of CD5 antigen on the surface of human peripheral B lymphocytes.

In this study, we investigated the expression of CD5 molecules on the surface of mature human peripheral B lymphocytes. Human CD5+ B cells were isolated from tonsils and peripheral blood. Their terminal differentiation into plasma cells was induced with IL-2. In the presence of this lymphokine, a subset of CD5+ B cells ceased to express CD5 proteins on their surface. When CD5+ B cells and non-B cells were removed from the suspension. CD5 antigens were spontaneously reexpressed on the surface of CD5- B cells. This suggests that the CD5- phenotype of a subset of B cells in these suspensions resulted from pressure(s) exerted on them by the other cellular components of the suspensions. B cells which have reexpressed membrane CD5 in the absence of CD5+ B cells and non-B cells retained their ability to reprogress to CD5- phenotype and to undergo terminal differentiation into plasma cells when stimulated with IL-2. A short exposure (4 hr) of CD5- B cells to 5 nM IL-2 resulted in the loss of their capability to spontaneously reexpress surface CD5 in the absence of other lymphoid cells. Taken together, these data suggest that the expression of CD5 antigens on B cell membrane is governed by a network-type balance between all cellular compartments within the suspension. Fluctuations of this equilibrium results in the shuttling of B cells between CD5+ and CD5+ phenotypes until they become irreversibly engaged in the terminal differentiation pathway. The interconversion CD5+<==>CD5- on B cell membrane does not argue for CD5 molecule as the marker of a distinct B cell lineage.

Antigens, CD↗
PubMed1989

In vitro modulation of leucocyte-function-associated antigen-1 expression on two leukemic cell lines.

Leukocyte-function-associated antigen-1 (LFA-1) expression on two widespread tumor cell lines: K562 (an erythroleukemia) and MOLT-4 (a T leukemia), was investigated using two monoclonal antibodies specific for the alpha chain of this surface antigen, and flow cytometry analysis. When K562 cells are in the exponential phase of growth, they display very low levels of LFA-1. By contrast, cells from the plateau phase exhibit a strong labelling, which disappears rapidly when they are allowed to resume division by changing the culture medium. Using the same experimental conditions, we failed to detect any LFA-1 expression on MOLT-4 cells. However, after stimulation of these cells by phorbol myristate acetate, we observed a significant labelling, which occurred within 2 days of treatment. The LFA-1 expression disappears progressively after removal of the phorbol ester. From these results it may be concluded that (a) LFA-1 expression can vary considerably according to the culture conditions, (b) the expression of this antigen on the surface of non-expressing variants can be induced by phorbol ester, and (c) in both cases, the change in expression can be reversed completely by replacing the culture medium or by removing phorbol myristate acetate from it.

Antigens, Differentiation↗
PubMed1987

Thyroid hormone modulates the expression of a neurofilament antigen in the cerebellar cortex: premature induction and overexpression by basket cells in hyperthyroidism and a critical period for the correction of hypothyroidism.

Neurofilament expression by basket cells of the cerebellar cortex is suppressed in hypothyroidism. By using a monoclonal antibody (mabN210) that selectively recognizes an epitope associated with the 210-kDa neurofilament subunit, we have explored the relationship between thyroid hormone levels and basket cell maturation. In animals rendered hypothyroid by inclusion of propylthiouracil in the maternal drinking water from embryo age E17, there is a complete absence of mabN210 immunoreactivity in the basket cell axons, while the other immunoreactive axons in the cerebellar cortex, primarily Purkinje cell axons and mossy fibers, are apparently unaffected. This deficit can be corrected by treatment with thyroid hormone but there seems to be a critical period for full recovery, for animals treated from birth recover normally whereas there is a gradual diminution in the efficacy of treatment the later it begins. Thyroid hormone therapy begun after postnatal day 30 (P30) leads only to very minor recovery. By contrast, animals on a hyperthyroid regime show premature mabN210-antigen induction in the basket cells and supranormal levels of expression at P25, despite the severe reduction in the number of basket cell somata. This suggests either abnormal compensatory sprouting of axon collaterals by the remaining basket cells or the occurrence, during normal cerebellar corticogenesis, of competition between basket cell axons for a limited number of Purkinje cell targets followed by the elimination of the excess collaterals.

Animals↗