Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Antigenic Modulation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 937 records · Page 52Linked to original sources
PubMed1995

Evidence that measles virus hemagglutinin initiates modulation of leukocyte function-associated antigen 1 expression.

Measles virus (MV), human immunodeficiency virus, Epstein-Barr virus, and other leukotropic viruses can modulate the expression of leukocyte function antigen 1 (LFA-1) on the surface of infected and nearby leukocytes. This ability to induce changes in LFA-1 expression may play an important role in the pathogenesis of these viruses. However, the mechanism(s) involved in virus-mediated regulation of LFA-1 is unknown. Evidence is presented in this report that it is the MV hemagglutinin (H) protein that initiates up-regulation of LFA-1 expression in leukocyte cultures infected with this virus. Indeed, comparison of the abilities of different MV strains to modulate LFA-1 expression, examination of published nucleotide sequences for the H proteins of different vaccine strains, and competitive inhibition assays using oligopeptides homologous or heterologous to a region of the H protein gene encompassing amino acid 116 (from the amino terminus) all suggest that it is this portion of the H protein that is responsible for MV-induced alteration of LFA-1. These comparisons also support the hypothesis that there is a relationship between the abilities of different MV strains to alter LFA-1 expression and their pathogenic potentials.

Amino Acid Sequence↗
PubMed1995

Differential effects of interleukin-10 on the expression of HLA class II and CD1 molecules induced by granulocyte/macrophage colony-stimulating factor/interleukin-4.

Interleukin (IL)-10 down-regulates HLA class II molecules, whether constitutively expressed or up-regulated by interferon-gamma or IL-4 on monocytes but not on B lymphocytes. In this study we show that IL-10 does not inhibit HLA class II expression induced by the combination granulocyte/macrophage colony-stimulating factor and IL-4 on monocytes, although it simultaneously abrogates the expression of CD1 molecules induced by the same combination of cytokines. CD1 molecules can act as element of genetic restriction for CD4- CD8- T lymphocytes, and the suppression of CD1 expression by IL-10 abolished antigen presentation to CD1-restricted CD4- CD8- T cell receptor-positive T cells. Although HLA class II expression was not down-regulated by IL-10, the antigen specific proliferative response of CD4+ T cells was nevertheless decreased. This was not caused by down-regulation of known co-stimulatory molecules such as B7.1, B7.2 and ICAM-1. IL-10 decreased the antigen specific proliferative response further by directly influencing the T lymphocytes. Our results indicate that IL-10 exerts some of its immunoregulatory functions by differential modulation of antigen presenting molecules, induced by the same combination of cytokines.

Antigen Presentation↗
PubMed1987

Host effector mechanisms against parasites.

The first part of this presentation considers some of the complexities of parasitic infections and parasite-specific effector mechanisms which have hampered the development of practical methods of immunisation against parasitic diseases. In the second part, an outline is given of the effector mechanisms involved in immunity of cattle to the protozoan parasite Theileria parva. Parasites are antigenically complex organisms which often have distinct developmental stages, sometimes with different predilection sites within the host. Antigenic polymorphism between strains is a common feature of parasites and sometimes results in strain-specific immunity. Certain parasites have also evolved mechanisms of modulating surface antigens which allow them to escape host effector mechanism. Effector mechanisms which control parasitic infections may operate by preventing establishment of the parasites, by eliminating the parasites once they have established or by affecting growth or fecundity of the parasites. In addition to specific antibody and cell-mediated immune responses, inflammatory or physiological responses play an important role in the control of some parasites. Current evidence suggests that effector mechanisms against T.parva parasites operate at two levels. First, antibodies produced against the infective stage of the parasite, the sporozoite, can, by neutralising infectivity, reduce the numbers of organisms which establish in the host. Second, cytotoxic T cells directed against parasitised lymphoblasts cause destruction of parasites following their establishment in the host. Moreover, in situations where immunity is parasite strain-specific, the cytotoxic T cell responses have also been found to be strain-specific. The elucidation of these effector mechanisms has indicated potential new strategies of immunisation against T.parva.

Animals↗
PubMed1987

Comparison of gamma-interferon and alloantigen-induced T cell factors in the induction of MHC class II antigen expression and in the modulation of the immunogenicity of lymphocyte-free rat bone marrow.

In a rat model, we compared the effects of various soluble products released by T cells, such as the unspecifically acting gamma-interferon or the newly detected alloantigen-induced factors that specifically act on nonlymphoid, hemopoietic bone marrow cells. We found two types of reactivity patterns with regard to the induction of MHC class II antigen expression on these cells. The very same patterns could be demonstrated when we investigated the modulation of their stimulatory capacity, i.e., their immunogenicity in a T proliferation assay. These findings are discussed in relation to the increasing incidence of immunologically mediated graft rejections in clinical bone marrow transplantation following T cell purging.

Animals↗
PubMed2003

Selective priming of Th1-mediated antigen-specific immune responses following oral administration of mixed prescriptions of traditional Korean medicines.

BACKGROUND: In previous studies, we showed that oral administration of traditional Korean medicines, Soamsan (SA) and Bo-yang-hwan-o-tang (BHT), modulated antigen-specific immune responses in mice. METHODS: We attempted to strengthen cell-mediated immune responses in mice using two mixed prescriptions composed mainly of components used in SA and/or BHT. The effect of oral administration of the medicines on the induction of antigen-specific immune responses was investigated using hen egg-white lysozyme (HEL) as a model antigen system. RESULTS: Following oral administration, HEL-specific cellular immune responses were enhanced in HEL low-responder mice, and the concentrations of gamma interferon (IFN-gamma), but not interleukin (IL)-4, increased significantly. In addition, the prescriptions decreased the level of HEL-specific antibodies of the immunoglobulin (Ig)G1 subtype, which is associated with helper T lymphocyte (Th2) cell stimulation. Moreover, the presence of the medicines in vitro significantly increased IFN-gamma production from mouse splenocytes, and the magnitude of the increase was closely associated with glycoprotein concentrations. CONCLUSIONS: The Korean prescriptions enhanced anti-HEL-specific cellular immune responses by selectively priming specific subtypes of the helper T cell population. Consequently, they might be useful therapy for patients who need enhanced Th1, or to suppress Th2 immune responses.

Animals↗
PubMed1992

Development and immunophenotyping of the pharyngeal tonsil (adenoid) in cattle.

Immunoperoxidase staining and electron and light microscopy were used to characterize the development of the pharyngeal tonsil in 98 cattle aged between 30 days of gestation and 12 years. The rugae of the pharyngeal tonsil were poorly formed before 95 days of gestation. Microvillous (M) cells associated with intra-epithelial leucocytes (lympho-epithelium) were scattered among ciliated and goblet cells covering most of the surface in post-natal animals. Intra-epithelial leucocytes were rare in fetuses, but ciliated and M cells could be distinguished. Leucocytes of the lamina propria started to accumulate at approximately 120 days of gestation. A loose accumulation of mononuclear cells progressed into a B-cell rich upper and T-cell rich lower layer, with typical lymphoid tissue organization in post-natal animals and lymphoid involution in aged cattle. Primary lymphoid follicles formed at 5 months of gestation, but germinal centres did not form until 2 to 4 weeks after birth. Except for null cells, the relative number of cells staining for each leucocyte phenotype or MHC class II antigen increased with age, especially during the neonatal period. The early development, strategic location and specialized structure of the pharyngeal tonsil suggest an important role in modulating inhaled antigens in cattle. Fetal and neonatal calves had minimal lymphoid tissue priming, as indicated by lack of secondary follicles, low MHC class II expression and few intra-epithelial leucocytes. The phenotypic differences may be relevant to the increased susceptibility of calves to infectious diseases shortly after birth.

Animals↗
PubMed1998

An ELISA for a multiphosphorylated peptide, alpha(s1)-casein(59-79).

Multiphosphorylated segments of proteins are predicted to be in or near epitopes. However, due to the very hydrophilic nature of multiphosphorylated peptides, epitope mapping by ELISA using conventional microtitre plates can produce false negatives due to poor antigen adsorption. We have developed a sensitive ELISA for a multiphosphorylated peptide alpha(s1)-casein(59-79) containing five phosphoseryl residues using Nunc-Immuno Maxisorp modules for antigen adsorption. The peptide alpha(s1)-casein(59-79) was detected in the ELISA at antigen coating concentrations of 1.0 microg/ml and above, using rabbit anti-casein antibodies at a dilution of 1/10,000 in Tris-buffered saline containing 0.05% (w/v) Tween 20 and 1.0% (v/v) normal goat serum. At an antigen coating concentration of 10 microg/ml, anti-casein antibodies bound to alpha(s1)-casein(59-79) and produced an absorbance of more than 100 times background. Using conventional polyvinyl chloride and polystyrene plates the peptide alpha(s1)-casein(59-79) could only be detected at very high antigen coating concentrations of 1-10 mg/ml. The addition of 0.05% (w/v) Tween 20 to the blocking, antibody diluting and wash buffers of the ELISA was shown to significantly reduce nonspecific binding of the primary antibody. Further, the inclusion of normal goat serum in the blocking and antibody diluting buffers resulted in a small but significant increase in absorbance. The ELISA developed in this study has been used successfully with a range of enzymatically derived and synthetic peptides containing one to five phosphorylated residues such that it should have general applicability to the study of antigenicity of multiphosphorylated peptides.

Amino Acid Sequence↗
PubMed2001

Modulation of CD45 tyrosine phosphatase activity by antigen.

CD45 is a widely distributed phosphatase which modulates the activity of Lck by controlling the phosphorylation status of two tyrosine residues localized in the catalytic activation loop and in the negative regulatory domain. Little is known about the regulation of CD45 activity upon T cell activation. In the present study, we found that, in resting lymphocytes, an enzymatically active fraction of CD45 molecules is associated to the CD4 coreceptor. TCR engagement by an agonist ligand markedly inhibited this pool of CD45 phosphatase without affecting the CD4 / CD45 association. These results reveal that the modulation of the CD4-associated CD45 phosphatase activity is a very early biochemical event triggered by TCR stimulation. Since the recruitment of CD4 is an initial step in the activation process, the inhibition of this pool of CD45 molecules would be crucial to prevent dephosphorylation of relevant substrates which promote the activation process.

Animals↗
PubMed2003

Suppression of myasthenia gravis by antigen-specific mucosal tolerance and modulation of cytokines and costimulatory factors.

We have shown that mucosal administration of recombinant fragments corresponding to the human acetylcholine receptor (AChR) alpha subunit suppresses chronic ongoing experimental autoimmune myasthenia gravis (EAMG) in rats. Treated animals exhibit a Th1 to Th2/Th3 shift in their cytokine profile and downregulation of costimulatory factors. However, application of a xenogeneic recombinant fragment may have limitations when considered as a possible approach for the treatment of MG in humans. We therefore tested the potential of a syngeneic fragment and of long synthetic peptides to suppress EAMG. We found that a syngeneic fragment corresponding to the extracellular region of the rat AChR alpha subunit was as effective as the formerly described human xenogeneic fragment in suppressing ongoing EAMG. This is encouraging in view of the potential use of mucosally administered recombinant AChR fragments for the treatment of MG in humans. However, in severely affected individuals, this antigen-specific approach may need to be supported by direct modulation of cytokines and costimulatory factors known to be involved in the pathogenesis of EAMG. To test the potential of this approach, myasthenic rats were injected by antibodies either to the proinflammatory cytokine IL-18 or to the costimulatory factor CD40L. These treatments act via different mechanisms, but both lead to the alleviation of clinical symptoms even when given at the chronic phase of EAMG. We suggest that antagonists to key cytokines and/or costimulatory factors be used to augment antigen-specific treatments of myasthenia such as mucosal administration of AChR recombinant fragments.

Animals↗
PubMed2002

Antibodies to neuron-specific antigens in children with autism: possible cross-reaction with encephalitogenic proteins from milk, Chlamydia pneumoniae and Streptococcus group A.

We measured autoantibodies against nine different neuron-specific antigens and three cross-reactive peptides in the sera of autistic subjects and healthy controls by means of enzyme-linked immunosorbent assay (ELISA) testing. The antigens were myelin basic protein (MBP), myelin-associated glycoprotein (MAG), ganglioside (GM1), sulfatide (SULF), chondroitin sulfate (CONSO4), myelin oligodendrocyte glycoprotein (MOG), alpha,beta-crystallin (alpha,beta-CRYS), neurofilament proteins (NAFP), tubulin and three cross-reactive peptides, Chlamydia pneumoniae (CPP), streptococcal M protein (STM6P) and milk butyrophilin (BTN). Autistic children showed the highest levels of IgG, IgM and IgA antibodies against all neurologic antigens as well as the three cross-reactive peptides. These antibodies are specific because immune absorption demonstrated that only neuron-specific antigens or their cross-reactive epitopes could significantly reduce antibody levels. These antibodies may have been synthesized as a result of an alteration in the blood-brain barrier. This barrier promotes access of preexisting T-cells and central nervous system antigens to immunocompetent cells, which may start a vicious cycle. These results suggest a mechanism by which bacterial infections and milk antigens may modulate autoimmune responses in autism.

Antigens↗
PubMed1997

L antigens of sheep red blood cell membranes and modulation of ion transport.

Sheep are polymorphic with respect to the intracellular Na+ and K+ concentrations of their erythrocytes. Erythrocytes of sheep of the high-K+ (HK) phenotype have high K+ and low Na+ concentrations; erythrocytes from sheep of the allelic low-K+ (LK) phenotype have abnormally low K+ and high Na+ concentrations. The difference is due to differences in rates of cation transport: higher Na+-K+ pump flux in HK cells and higher K+-Cl- cotransport in LK cells. The HK/LK polymorphism is associated with a polymorphism of red blood cell antigens: the L antigen is only on LK cells, and HK cells have only the M antigen. There are two classes of L antigen that assort together: Lp, which is associated with Na+-K+ pumps, and Ll, which is associated with K+-Cl- cotransporters. There are functional consequences of these associations: anti-Lp antibody stimulates the pump and anti-Ll antibody inhibits cotransport. The use of these antibodies has permitted delineation of the roles of the antigens in modulating the function of the transporters. In this review, we summarize the evidence that these antigens are entities distinct from the pump. The Lp antigen reacts reversibly with the Na+-K+ pump; the antigen inhibits the pump, mainly by promoting nonspecific inhibition by intracellular K+. The antigen also modulates pump differentiation in immature cells. In contrast, the Ll antigen stimulates K+-Cl- cotransport. The evidence suggests that the two polymorphisms are controlled by a single genetic locus and that all of the distinct properties of ion transporters in LK cells are attributable to interactions with L antigens.

Animals↗
PubMed2003

Regulation of viral and autoimmune responses.

We have studied the induction and effector function of Th2-like regulatory cells in mouse models for type 1 diabetes (NOD and RIP-LCMV). CD4+ lymphocytes with specificity for insulin can be induced by immunization with the insulin B chain via the oral route or by DNA vaccination. Such cells are protective upon adoptive transfer and prevent diabetes development in syngeneic pre-diabetic recipients. In comparison to non-regulatory insulin B-specific cell lines, they produce high amounts of interleukin (IL)4 and IL10, whereas interferon (IFN)gamma and tumour necrosis factor (TNF)alpha levels are comparable. Indeed, IL4 is essential for the protective capability, as evidenced by use of IL4-deficient mice and sorting of IL4+ versus IL4- lymphocytes prior to transfer. Mechanistically, these cells act as bystander suppressors in the pancreatic draining node, the location where their cognate antigen, insulin B, is presented during the pre-diabetic inflammatory process. As a consequence, the autoaggressive response is locally dampened. We propose that this is achieved by modulation of antigen presenting cells that lose the ability to propagate aggressive responses after exposure to IL4 or IL10 in vitro. The clinically attractive side of our strategy is that it only acts as the site of inflammation, thus circumventing systemic side effects. In order to avoid induction of insulin B-specific autoaggressive T cells we have demonstrated that administration of IL4 or IL10 at the time of immunization is beneficial and therefore should be part of a potential future clinical application. Interestingly, these Th2-like regulators share in our systems no features with the so-called CD25+ regulatory cells, whose antigen specificity is still unclear. However, we have recent evidence that virus specific CD25+ cells can be generated and are able to affect antiviral responses in vivo.

Animals↗
PubMed1996

Sensitization of T-cell receptor-alpha beta+ T cells recovered from long-term T-cell receptor downmodulation.

Although the survival of fully allogeneic skin grafts was prominently prolonged by adult thymectomy in anti-T-cell receptor-alpha beta monoclonal antibody (TCR-alpha beta mAb)-treated mice compared with that of non-adult thymectomized (ATX) mice, the skin allografts were eventually rejected. In the anti-TCR-alpha beta mAb-treated ATX mice, as shown in the present study, most of TCR-alpha beta+ cells were promptly activated on day 2 and then rapidly disappeared by day 7, but some TCR-alpha beta- Thy-1+ cells remained at that time. These TCR-alpha beta- Thy-1+ cells which have downmodulated their TCR-alpha beta expression may be refractory to depletion events by the mAb treatment. Although these downmodulated T cells re-expressed their TCR-alpha beta on day 50, they could not respond to stimuli via TCR such as TCR cross-linking or alloantigens. However, they recovered the reactivity to donor antigens on day 85. These results indicate that the downmodulated T cells by anti-TCR-alpha beta mAb treatment are long-lived and re-express their TCR-alpha beta at a late stage to be sensitized to donor antigen, which suggests that additional regimens may be required to get permanent, or very long-term, graft acceptance.

Animals↗
PubMed1999

[Acyclovir may modulate clonal expansion of cd8+ lymphocytes induced by the Cytomegalovirus antigen].

BACKGROUND: Although the potent antiviral effect of acyclovir on the Herpes-simplex (HSV) and Varicela-zoster (VZV) virus and the scarce effectiveness versus Cytomegalovirus (CMV) is known, some data suggest that it may have an immunodulator implicated in the control of these viral disease. The aim of this study was to characterize this possible effect of acyclovir versus the CMV antigen. METHODS: We stimulated cultures of mononuclear cells obtained in 7 healthy patients who were seropositive for CMV and HSV with CMV antigen, HSV and with phitohemaglutinine (PHA). The proliferation index and culture cell phenotype were later determined in the absence and presence of acyclovir (2 micrograms/ml). In another group the proliferation index and cell phenotype following stimulation with the CMV antigen were studied prior to and after treating the same volunteers with acyclovir for one week (800 mg/6h). RESULTS: The CMV antigen and HSV induced T cell proliferation predominantly involving the CD8+ subpopulation leading to an inversion of the CD4/CD8 quotient. On addition of acyclovir to the cell culture a moderate reduction was produced in lymphoproliferative response versus the CMV antigen and HVS, characteristically modulating CD8+ cell proliferation, thereby leading to reestablishment of the CD4/CD8 quotient. However, the proliferation induced by PHA was not inhibited. These results were produced on oral administration of acyclovir. CONCLUSIONS: Acyclovir modulates the lymphoproliferative response induced by CMV antigen. Based on this observation, the authors hypothesize that this immunomodulation may be related to its preventive effect on CMV disease in transplanted patients.

Acyclovir↗
PubMed2004

Ser-123 of the large antigen of hepatitis delta virus modulates its cellular localization to the nucleolus, SC-35 speckles or the cytoplasm.

Hepatitis delta virus (HDV) is a defective virus and requires hepatitis B virus (HBV) to supply envelope proteins (HBsAg) for maturation and secretion. It is known that two proteins produced by HDV, the small (SDAg) and large (LDAg) antigens, are located in the nucleolus, speckles and the cytoplasm and are involved in genome replication and virion packaging. However, little is known about how they are targeted to the specific sites where they act. A green fluorescence protein fused to LDAg (GFP-LD) has been shown previously to translocate from the nucleolus to SC-35 speckles in the presence of the casein kinase II inhibitor dichlororibofuranosyl benzimidazole. In this study, we determined which amino acids of GFP-LD were responsible for the translocation from the nucleolus to SC-35 speckles and created three GFP-LD derivatives, GFP-LDS2A, GFP-LDS123A and GFP-LDS2/123A. Fluorescence microscopy studies showed that Ser-123 mutants had a high tendency to target SC-35 speckles in both transfected HeLa and HuH-7 cells and suggested that Ser-123, but not Ser-2, plays a role in modulating LDAg translocation to the nucleolus or to SC-35 speckles. This study also demonstrated that HBsAg plays a role in facilitating the transportation of LDAg from the nucleus to cytoplasm. Compared with GFP-LD and GFP-LDS2A, mutants of Ser-123 were less efficiently transported to the cytoplasm and resulted in a lower level of secretion. In contrast, little or no isoprenylation mutant was observed in the cytoplasm of HuH-7 cells expressing HbsAg, suggesting that the isoprenylation of LDAg plays a role in export from the nucleus. Thus, the current study demonstrated that both cis and trans elements modulate HDAg translocation to various subcellular sites.

Active Transport, Cell Nucleus↗
PubMed1998

Immunomodulation induced by Ascaris suum extract in mice: effect of anti-interleukin-4 and anti-interleukin-10 antibodies.

Simultaneous immunization of mice with an Ascaris suum extract (Asc) and ovalbumin (OA) markedly affects the immune response to OA. The role of interleukin (IL)-4 and IL-10 induced by Asc immunization on the modulation of antigen-specific and mitogen-induced responses was investigated following single or combined cytokine-specific monoclonal antibody (MoAb) treatment of mice before immunization with OA + Asc. Immediate hypersensitivity reactions to aggregated OA and OA-specific immunoglobulin (Ig)G2a antibody production were completely restored only when both IL-4 and IL-10 were neutralized. These findings were associated with enhanced interferon (IFN)-gamma secretion by OA-stimulated lymph node (LN) cells. In addition, the Asc-specific cytokine response in anti-IL-4 plus anti-IL-10 MoAb treated mice was shifted towards a Th1 phenotype, with an increase in IFN-gamma and IL-2 levels and a decrease in IL-4, but not in IL-10, levels. Consequently, Asc-specific IgG2a antibody production increased, whereas IgE titres diminished in these animals. These results indicate that IL-4 and IL-10 act together in the Asc-induced mechanism of antigen-specific pansuppression. In contrast, modulation of Concanavalin A (Con A)-induced cytokine responses in Asc-immunized mice appears to be essentially mediated by an IL-4-dependent mechanism, since the neutralization of just IL-4 (and not of IL-10), either in vivo or in vitro, changed the cytokine profile from a Th2 towards a Th1 type. However, OA and Asc-specific cell responses were not modified by either anti-IL-4 or by anti-IL-4 + anti-IL-10 MoAbs in vitro treatments, suggesting that the induction of a Th2 response to Asc components concomitant to OA immunization has a strong suppressive effect on the priming stage of OA-specific Th1 type response.

Adjuvants, Immunologic↗
PubMed1999

Altering the cellular location of an antigen expressed by a DNA-based vaccine modulates the immune response.

The potential for DNA vaccines encoding mutated versions of the same antigen to modulate immune responses in C3H/HeN mice was investigated. We created expression plasmids that encoded several versions of glycoprotein D (gD) from bovine herpesvirus 1, including authentic membrane-anchored glycoprotein (pSLRSV.AgD), a secreted glycoprotein (pSLRSV.SgD), and an intracellular protein (pSLRSV.CgD). Immunization of an inbred strain of mice with these plasmids resulted in highly efficacious and long-lasting humoral and cell-mediated immunity. We also demonstrated that the cell compartment in which plasmid-encoded gD was expressed caused a deviation in the serum immunoglobulin (Ig) isotype profile as well as the predominant cytokines secreted from the draining lymph node. Immunization of C3H/HeN mice with DNA vaccines encoding cell-associated forms of gD resulted in a predominance of serum IgG2a and gamma interferon-secreting cells within the spleens and draining lymph nodes. In contrast, mice immunized with a secreted form of this same antigen displayed immune responses characterized by greater levels of interleukin 4 in the draining lymph node and IgG1 as the predominant serum isotype. We also showed evidence of compartmentalization of distinct immune responses within different lymphoid organs.

Animals↗