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Results for “Antigenic Modulation”

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At least 1,225 records · Page 68Linked to original sources
PubMed2007

Soluble mannosylated myelin peptide inhibits the encephalitogenicity of autoreactive T cells during experimental autoimmune encephalomyelitis.

We have previously shown that immunization with a mannosylated myelin peptide in complete adjuvant induces tolerance instead of disease in experimental autoimmune encephalomyelitis (EAE), a rodent model for multiple sclerosis. In this report we demonstrate that treatment with a soluble mannosylated epitope of proteolipid protein (M-PLP(139-151)) significantly inhibits disease mediated by autoreactive myelin-specific T cells during EAE. Treatment with M-PLP(139-151), applied in different EAE models, significantly reduced the incidence of disease and the severity of clinical symptoms. Delayed-type hypersensitivity responses were abolished after peptide treatment, emphasizing the impact on peripheral T-cell reactivity. Histological analysis of spinal cord tissue from mice treated with M-PLP(139-151) revealed the presence of only few macrophages and T cells. Moreover, little expression of interferon-gamma, interleukin-23, or major histocompatibility complex class II antigen was detected. Immune modulation by M-PLP(139-151) was primarily antigen-specific because an irrelevant mannosylated peptide showed no significant effect on delayed-type hypersensitivity responses or on the course of EAE. Therefore, mannosylated antigens may represent a novel therapeutic approach for antigen-specific modulation of autoreactive T cells in vivo.

Animals↗
PubMed1996

Human antibodies against the polymorphic epithelial mucin in ovarian cancer patients recognise a novel sequence in the tandem repeat region.

The humoral immune response to the polymorphic epithelial mucin (PEM) was studied by characterising the reactivity of human antibodies generated by EBV-immortalised B-cells from tumour-draining lymph nodes of ovarian cancer patients. All the human antibodies, selected in ELISA for their reactivity to the protein tandem core repeat sequence, reacted with PEM-expressing tumour cells. Aberrant glycosylation of the peptide core of the PEM molecule in cancer cells leads to the exposure of peptide epitopes that can be considered tumour specific. The epitope mapping of six human antibodies revealed that only one of them contained the PDTR sequence, shown to be the immunodominant epitope in the mouse. Four of the six human antibodies recognised a novel common immunogenic sequence (APPAH) in the tandem repeats. The binding of these human antibodies did not appear to be modulated by the length of the carbohydrate side chains, as shown by O-glycosylation inhibition studies. These results indicate that distinct sequences within the tandem repeat of PEM are target for a humoral immune response in humans. The presence of antibodies directed against different epitopes within the same antigenic region may modulate the antigen presentation process and the ongoing immune response. This data may help in clarifying the mechanisms of the immune response to PEM in cancer patients for the development of PEM-based immunotherapy.

Antibodies, Neoplasm↗
PubMedDate not supplied

Dendritic cells produce eicosanoids, which modulate generation and functions of antigen-presenting cells.

Eicosanoids have been shown to be potent immunoregulatory arachidonic acid (AA) metabolites. AA is the precursor of prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)) which are able to modulate both inflammation and the immune response. Dendritic cells process and present antigens to T lymphocytes. They are highly specialized antigen-presenting cells (APC) and usually considered as 'professional APC'. In the present paper, we report some data on the biosynthetic capacity of murine APC from the bone marrow (BM-DCs) to produce AA metabolites. Using an ELISA we have observed that BM-DCs spontaneously produce both PGE(2) and LTB(4) whose production increased in response to bacterial lipopolysaccharides (LPS). In addition we found that LTB(4) production was twice as high when both COX pathways were blocked with selective COX-inhibitors. We have also investigated the effect of PGE(2) and LTB(4) on the in vitro generation of the so-called BM-DCs. Exogenous PGE(2) and LTB(4) added to bone marrow cultures inhibit and promote, respectively, BM-DC generation. PGE(2) added to the maturing BM-DCs reduces their MHC class-II expression.

Animals↗
PubMed1982

Factors that modulate clearance and ultimate fate of a specific schistosome antigen (GASP) in schistosome infections.

To understand factors that modulate the amount and removal of antigen found in the circulation of schistosome-infected mice, a specific schistosome antigen, GASP, found in the circulation of infected animals, was radiolabeled with Bolton-Hunter reagent and injected into infected and control mice. The rates of clearance, levels of antigen binding, and the fate of the injected antigen were determined. Within 1 to 3 wk after injection, infected animals developed enhanced antigen clearance that paralleled the increase in antibody to GASP. Lightly infected animals showed faster clearance rates and increased antibody levels compared with heavily infected mice. The level of antibody in the sera, irrespective of the duration or intensity of infection, correlated with enhanced clearance. Heavily infected animals removed preformed immune complexes as rapidly as lightly infected mice. This indicates that the relative inability to clear antigen was not due to blockade of Kupffer cells. Circulating GASP antigen, determined by countercurrent electrophoresis, was detected in heavily infected animals in the presence of increased antibody, suggesting that circulating GASP was in immune complexes. Both free and complexed antigen were primarily cleared by the liver and then excreted in the urine as low m.w. nonantigenic products. With sensitive radioimmunoassays, GASP could not be detected in infected human or mouse urine.

Animals↗
PubMed1976

The effect of specific antiserum on the metabolism of three membrane-associated antigens of ASL-1 x LM(TK)- hybrid cells.

Fusion of ASL-1 cells, a murine leukemia forming thymus leukemia (TL) antigens, with LM(TK)- cells, a TL(--) murine cell line, resulted in a stable hybrid forming TL antigens. The hybrids failed to undergo modulation, the reversible dissappearance of TL antigens from the surfaces of the cells, stimulated by TL antiserum. Unlike ASL-1 cells, the rate of disappearance of the antigens from modulation negative hydrid cells was unaffected by TL antiserum. The t 1/2 of TL antigens of the hybrid was approximately 30 h. The t 1/2 of TL antigens of ASL-1 cells was 10 h in the presence of TL antiserum, 18 h in the absence of TL antiserum. The rate of metabolism of a putative tumor-associated antigen of ASL-1 cells formed by the hybrid was unaffected by exposure to specific antiserum, as was the metabolism of H-2 antigens formed by the cell types.

Animals↗
PubMed1975

Immunity to murine sarcoma virus induced tumours. IV. Direct cellular cytolysis of 51Cr labelled target cells in vitro and analysis of blocking factors which modulate cytotoxicity.

The antigen specific cell mediated cytotoxicity of MSV immune spleen lymphocytes to 51Cr labelled murine lymphoma cells was wholly abolished by pretreatment of the spleen cells with anti-theta antibody and complement. Early during the immune response to MSV the cytotoxic acitivity was inhibited by incubation of immune lymphocytes with "late progressor" or "early regressor" serum. Immune lymphocytes at later times were more refractory to such inhibition by serum blocking factors. Although unfractionated cytotoxic lymphocytes, irrespective of the time after MSV infection at which they were tested, were inhibited by soluble tumour associated antigen (TAA), a subpopulation of cytotoxic T cells was identified which was inhibited neither by antigen nor serum.

Animals↗
PubMed2003

Portal to the interior: viral pathogenesis and natural compounds that restore mucosal immunity and modulate inflammation.

Most antigens, particularly viruses, enter the body through the mucosal epithelia where they are carried by afferent lymphatics to regional lymph nodes for presentation to the immune system. Although they share immunological similarities, immune processes that protect the mucosa are distinct from innate and acquired immunity. The barrier formed by the intestinal mucosa is the most studied, with its microenvironment having a marked influence on both local and systemic immune responses. A healthy microenvironment and resilient neighboring tissue provide protection against inflammation known to dampen mucosal immunity, promote carcinogenesis, contribute to systemic inflammatory processes, and result in autoimmune diseases. Numerous natural substances improve this microenvironment and thereby enhance immunity against microbial infections. Since mucosal immunity forms the first line of defense against many commonly transmitted pathogens, restoring and maintaining mucosal immunity is critical for disease prevention and intervention. This article discusses the nature of mucosal immunity and its relationship to viral infections and other conditions, and reviews natural compounds that help restore mucosal immunity.

Dietary Supplements↗
PubMed1986

Modulation in vivo of Lyt 2 antigen expression on T cells by anti-Lyt 2 antibody: effects on Con A-induced unresponsiveness.

After a series of intraperitoneal injections of rat monoclonal anti-Lyt 2 antibody supernatant, BDF1 mice showed a loss of cells bearing Lyt 2 surface antigens but no reduction in the numbers of T cells in the spleen. With overnight culture in vitro, splenic T cells from anti-Lyt 2-treated mice regenerated surface Lyt 2, with the proportion of Lyt 2+ cells returning to control levels. Anti-rat IgG antibody was found in the serum of mice that had received the anti-Lyt 2 treatments. Modulation of the surface Lyt 2 antigens was demonstrable in vitro but only in the presence of mouse anti-rat IgG antibody. Functionally, this series of in vivo anti-Lyt 2 antibody treatments substantially reversed Con A-induced suppression of the anti-sheep red blood cell antibody response.

Animals↗
PubMed2000

Maturation of an antibody response is governed by modulations in flexibility of the antigen-combining site.

Although affinity maturation constitutes an integral part of T-dependent humoral responses, its structural basis is less well understood. We compared the physicochemical properties of antigen binding of several independent antibody panels derived from both germline and secondary responses. We found that antibody maturation essentially reflects modulations in entropy-control of the association, but not dissociation, step of the binding. This influence stems from variations in conformational heterogeneity of the antigen-combining site, which in turn regulates both the affinity and specificity for antigen. Thus, the simple device of manipulating conformational flexibility of paratope provides a mechanism wherein the transition from a degenerate recognition capability to a high-fidelity effector response is readily achieved, with the minimum of somatic mutations.

Amino Acid Sequence↗
PubMedDate not supplied

Expression of tumor-associated Thomsen-Friedenreich antigen (T Ag) in Helicobacter pylori and modulation of T Ag specific immune response in infected individuals.

We tested the hypothesis that the gastric cancer associated bacteria, Helicobacter pylori (H. pylori) express the cancer-related Thomsen-Friedenreich (T) antigen. We also analysed whether infection with H. pylori alters the amount of natural anti-T antibodies in the patients' sera. Cell surface membrane extracts of H. pylori NCTC 11637 strain and clinical isolates of H. pylori (n = 13) were analysed by immunoblotting and cell-ELISA with five different T antigen-specific monoclonal antibodies (MAbs). Two major protein bands of approximately 68 kDa and 58 kDa were immunostained on blots of H. pylori extracts with T specific MAbs but not immunostained with unrelated MAb. The specificity was shown in that immunostaining was blocked with peanut agglutinin (PNA) and rabbit antiserum to T antigen. The binding of T specific MAb to the 58 kDa protein band was also blocked by rabbit antiserum against heat shock proteins of H. pylori. The relative expression of T antigen-related proteins differed among H. pylori strains, with 68 kD associated T antigen expression higher in patients with more severe pathology. The level of IgG antibody to T epitope in patients with gastric cancer (n = 66) and normal blood donors (n = 62) were compared and the level of anti-T Ab in gastric cancer patients was significantly lower than that in normal blood donors. A significant positive correlation between T specific antibody in serum and H. pylori IgG antibody level was found in H. pylori-infected normal blood donors (P < 0.001), but this correlation was not found in H. pylori-infected cancer patients. In summary, the cancer related T epitope is expressed in H. pylori and modulation of T antigen-specific immune response in H. pylori-infected individuals suggests that H. pylori infection may alter natural immune mechanisms against cancer.

Animals↗
PubMed1993

Different mechanisms regulate the monoclonal antibody-induced modulation of CD2, CD3, and CD5 in human lymphocytes.

The CD2, CD3, and CD5 antigens are down-modulated from the cell surface of peripheral blood mononuclear cells after a 24-hr incubation with specific monoclonal antibodies (mAb). Here we show that active (phorbol myristate acetate, phorbol dibutyrate acetate, and mezerein) but not inactive (4 beta-phorbol) tumor-promoting agents inhibit the mAb-induced modulation of CD2 and CD5, but not CD3, without concomitant changes in the surface distribution of these antigens (such as capping). This inhibitory effect is not protein synthesis dependent and is reversed by protein kinase C inhibitors (staurosporine and H-7). The use of cytoskeleton-disrupting agents shows the existence of different cytoskeletal interactions driving the mAb-induced modulation of CD2 and CD5 with respect to CD3. Treatment with cytochalasin D (an agent that inhibits microfilament polymerization) but not colchicine (an agent that inhibits microtubule polymerization) reproduced the effect of TPA on the mAb-induced modulation of CD2, CD3, and CD5. Our results indicate that the mAb-induced modulation of CD2 and CD5 is dependent on microfilament (namely actin) polymerization and PKC activation, while the modulation of CD3 is not.

Antibodies, Monoclonal↗
PubMed1998

Coadministration of IL-12 or IL-10 expression cassettes drives immune responses toward a Th1 phenotype.

Cytokines are important regulators of the immune response. They influence immune expression, the development of immunologic memory, and regulation of antigen-specific and nonspecific immune activation as well as allergic responses. In a model system in mice, we have studied the effect of plasmids expressing interleukin (IL)-10 or IL-12 on the modulation of antigen-specific responses. Coadministration of IL-12 or IL-10 genes with DNA immunogens directed the antigen-specific immune response toward a T helper (Th1)-type immunity. In addition to the modulation of antigen-specific immune responses, we studied the induction of delayed-type hypersensitivity (DTH) to contact allergens as an in vivo model of the Th1 response. We found that IL-12 and IL-10 gene-containing plasmids, and not the bacterial plasmid alone, upregulate this response. Our cytokine gene delivery technique demonstrates an important level of control of the magnitude and direction of induced immune responses and could be advantageous in a wide variety of immunotherapeutic strategies.

Animals↗
PubMed2001

Dexamethasone modulates TCR zeta chain expression and antigen receptor-mediated early signaling events in human T lymphocytes.

Dexamethasone is a potent anti-inflammatory and immunosupressive agent that has complex, yet incompletely defined, effects on the immune response. Here, we explored the effect of dexamethasone on the expression of TCR zeta chain and TCR/CD3-induced early signaling events in human T lymphocytes. Immunoblotting studies using TCR zeta chain specific mAb showed a dose-dependent biphasic effect of dexamethasone on TCR zeta chain expression, that is, it was increased when cells were incubated with 10 nM, whereas the expression was decreased when incubated with 100 nM dexamethasone. The dose-dependent biphasic effect of dexamethsone on the TCR zeta chain expression was also revealed by FACS analysis of permeabilized cells. Time course studies showed that upregulation of the TCR zeta chain at 10 nM dexamethasone reached maximum levels at 24 h and remained elevated up to 48 h. Other subunits of the TCR/CD3 complex were minimally affected under these conditions. The increased expression of the TCR zeta chain following treatment with 10 nM dexamethasone correlated with increased anti-CD3 antibody-induced tyrosine phosphorylation of the TCR zeta chain and downstream signaling intermediate ZAP-70 and PLC gamma with faster kinetics. Similarly, the induction of TCR zeta chain expression at 10 nM dexamethasone correlated with increased and more sustained TCR/CD3-mediated [Ca(2+)](i) response. Reporter gene assays using TCR zeta chain promoter-driven luciferase gene constructs in Jurkat cells showed that treatment with 10 nM dexamethasone increased TCR zeta chain promoter activity and that the region between -160 and +58 was responsible for the observed effect. These results suggest that dexamethasone primarily acts at the transcriptional level and differentially modulates TCR zeta chain expression and antigen receptor-mediated early signaling events in human peripheral T lymphocytes.

Adolescent↗
PubMed1996

Differential modulation by interferon gamma of the sensitivity of human melanoma cells to cytolytic T cell clones that recognize differentiation or progression antigens.

Human melanoma is a highly immunogenic tumor capable of inducing a specific immune response. A number of melanoma-associated antigens have been characterized during the past several years and can be classified into two groups: differentiation antigens-present also in normal melanocytes-and tumor-specific antigens, which, with the exception of testis, are present only in tumor cells. In a previous publication [Kirkin A. F., Petersen T. R., Olsen A. C., Li L., thor Straten P., Zeuthen J. (1995) Cancer Immunol Immunother 41:71] we have described the production of clones of cytotoxic T lymphocytes (CTL) against the highly immunogenic human melanoma cell line FM3. Using these clones we have defined four previously unknown melanoma-associated antigens, which could be subdivided into differentiation and progression antigens. In the experiments reported in this paper, we have further compared CTL clones from different groups and shown that the sensitivity of melanoma cells to CTL that recognize differentiation or progression antigens is differentially modulated during tumor progression as well as by the lymphokines interferon gamma (IFN gamma) and interleukin-10 (IL-10). The interaction of CTL clones recognizing progression antigens was strongly increased after treatment of melanoma cells with IFN gamma, while the recognition by CTL clones specific for differentiation antigens either was unchanged or significantly decreased. IL-10 treatment of melanoma cells induced up-regulation with respect to recognition by CTL clones specific for differentiation antigens without affecting the recognition of melanoma cells by CTL clones specific for progression antigens. Using cellular systems at different stages of tumor progression, we demonstrated that the progressed state of melanoma cells is associated with increased sensitivity to recognition by CTL clones detecting progression antigens, and with decreased sensitivity to CTL clones recognizing differentiation antigens. Mimicking tumor progression, treatment with IFN-gamma induced apparent down-regulation of differentiation antigens. A hypothesis is suggested in which IFN-gamma plays different roles in the immune response against poorly immunogenic and highly immunogenic melanoma cells, increasing the progression of poorly immunogenic tumor cells or promoting a strong immune response and regression of highly immunogenic melanoma cells.

Animals↗
PubMed1979

Antibody-induced modulation of Friend virus cell surface antigens decreases virus production by persistent erythroleukemia cells: influence of the Rfv-3 gene.

The Rfv-3 gene was found to influence the level of Friend leukemia virus production in spleens of leukemic mice later than 30 days after virus inoculation. Rfv-3r/s mice [(B10.A X A)F1 and (B10.A X A.BY)F1] had decreased spleen virus levels 30-90 days after virus inoculation compared to Rfv-3s/s mice [A.BY, A, BALB.B, and (BALB/c X A)F1)]. In (B10.A X A)F1 X A backcross mice the spleen virus titer segregated with the level of viremia. The Rfv-3 gene appeared to act by controlling anti-Friend virus antibody production. The interaction of antiviral antibody with infected cells led to a decrease in release of infectious virus by late leukemic spleen cells in Rfv-3r/s mice to 1/300th that in Rfv-3s/s mice. This decrease in virus release appeared to be due to interference with the virus budding process due to antibody-mediated modulation of virus-induced cell surface antigens.

Animals↗
PubMed2001

Modulation of the immune response by systemic targeting of antigens to lymph nodes.

Factors that determine the immunogenicity of an antigen in vivo are still largely unknown. Direct administration of antigens into lymphatic organs appears to enhance immune response. We hypothesized that systemically targeting antigens to lymphatic tissue in vivo might modulate immunity. To test this hypothesis, we measured the humoral immune response elicited by bacteriophage vaccination. We show that the responses against a lymph node-targeted phage are significantly higher than those against control untargeted phage; the effect is specific because it is inhibited by coadministration of the cognate synthetic peptides displayed. Our data suggest that systemic targeting of antigens to lymph nodes through the circulation modulates humoral immune response. This strategy may have broad applications in the development of vaccines, production of antibodies, and immunotherapy.

Animals↗
PubMed1986

Epithelial modulation of tracheal smooth muscle response to antigenic stimulation.

The role of the epithelium has been studied in the contractile responses of rat trachea. The different modulations observed are discussed in respect to vagal components of the epithelial layer. Responses of rat trachea to immunologic stimulation are shown to be dependent on the presence of the epithelium, which prolongs the relaxation stage without affecting the contractions. This prolongation is abolished by neonatal capsaicin pretreatment, whereas substance P induces a significantly greater relaxation of serotonin-precontracted intact than deepithelialized trachea. Serotonin concentration-response curves are shifted to the right in intact preparations, which is partly reversed by neonatal capsaicin pretreatment, but a hyporeactivity of the tissue exists. A relaxing factor released by the epithelium is hypothesized, possibly dependent on substance P-ergic innervation. Muscarinic cholinergic innervation slightly modulates the contractions but not the relaxations in antigen-induced responses, independently on the presence of the epithelial layer. 4-Aminopyridine induces epithelium-dependent potentiations of contractions to antigen and to serotonin, which involves acetylcholine at one step of the reaction cascade. Epithelial-dependent contracting and relaxing factors are thus suggested in rat trachea.

4-Aminopyridine↗