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 919 records · Page 51Linked to original sources
PubMed1990

Modulation of expression of MHC antigens in the kidneys of mice by murine interferon-alpha/beta.

We have analyzed the effects of interferon-alpha/beta on MHC expression in the murine kidney, and compared these results with the MHC modulating effects of interferon-gamma. Natural murine interferon-alpha/beta was administered to B10.BR mice (H-2k), i.p., twice daily for 3 days. Expression of MHC antigens was assessed on day 4 by immunoperoxidase staining with biotinylated monoclonal antibodies to class I (KkDk) and class II (I-Ak) antigens. Interferon-alpha/beta significantly decreased the number of class II-positive renal cortical dendritic cells from 62.0/mm2 to 12.6/mm2 (P less than 0.001). A similar but less dramatic decrease was seen in cardiac dendritic cells. Little or no change in class II expression was observed in proximal tubules or glomeruli. Interferon-alpha/beta induced marked class I staining in the glomerulus, arterial endothelium, and Bowman's capsule. Proximal tubule cells also showed increased class I expression, but were less responsive than glomeruli. Thus, the effects of interferon-alpha/beta contrast with those of interferon-gamma, which increases class II expression on proximal tubules, induces relatively more class I expression in proximal tubules than glomeruli, and increases class II-positive dendritic cells. Furthermore, these results suggest that treatment with interferon-alpha/beta may have a complex effect on the immune response to a renal allograft due to its differential effects on class I and class II cell surface expression.

Animals↗
PubMed1991

Expression of major histocompatibility complex and HIV antigens within the brains of AIDS patients.

HIV establishes a chronic infection in the central nervous system (CNS) of AIDS patients. The immunopathogenesis of this chronic encephalitis is unknown. Because of the importance of major histocompatibility (MHC) class I and class II antigens in modulating the immune response, we examined the tissue expression of MHC molecules in relation to CNS damage and expression of viral antigens. By immunocytochemical staining we found that beta 2-microglobulin (beta 2M) expression is elevated in all cases with signs of viral encephalitis. beta 2M was expressed at high levels on endothelial cells, macrophages and possible oligodendroglia within regions of histopathology. In histologically normal regions elevated expression of beta 2M was noted only on endothelial cells. MHC class II expression was elevated only in the HIV encephalitis cases, and was restricted to macrophages/microglia and occasional endothelial cells. When compared with other viral encephalitides these findings suggest that the intra-CNS immune response to HIV is appropriate for viral presentation; however, the absence of responsive systemic T cells may lead to chronic viral infection.

AIDS Dementia Complex↗
PubMed1978

The acquisition and loss of antigen-specific cellular immune responsiveness in acute and chronic schistosomiasis in man.

To characterize the development and evolution of cellular immune responsiveness in individuals infected with the parasite Schistosoma mansoni, we studied fifteen patients with acute, subacute and chronic schistosomiasis. Lymphocytes from the three acutely infected patients responded vigorously to schistosome antigens in an in vitro blastogenic assay. By contrast, cells from nine chronically infected individuals were essentially unreactive to these same antigens. Patients infected for an intermediate period of time (9 months) generated responses between those of acute and chronic patients. The diminished responsiveness of chronically infected individuals was specific for schistosome antigens and did not extend to humoral immune responses. Following treatment of the infection with niridazole, these patients temporarily regained responsiveness to schistosome antigens. From these data we speculate that during the course of this parasitic helminth infection there develops a progressive and specific modulation of antigen recognition and proliferation by lymphocytes to schistosome antigens, and that such diminished immune reactivity may be important in maintaining the unique biological relationship which exists between a host and its parasites.

Acute Disease↗
PubMed1997

Expression and modulation of the Lewis x antigen (CD15) on the T cell line Molt-4.

The T cell lines Molt-4 and H9 exhibited a characteristic distribution of the cell adhesion molecule Lewis x (CD15, lacto-N-fucopentanose III) showing an unusually broad peak by flow cytometry ranging from cells without CD15 to cells with high expression. The cytokines IL-1, IL-2, IFN-beta, IFN-gamma, and TNF-alpha, known to activate T cells, did not affect CD15 expression. However, phorbol myristate acetate and the thymic peptide extract Thymex-L were able to enhance both the number of CD15-positive cells and the median fluorescence. The effects of both inducers were dose- and time-dependent. An additive or synergistic effect was not seen. These data suggest that phorbol esters and distinct thymic peptides can modulate the expression of the cell surface antigen CD15.

Adjuvants, Immunologic↗
PubMed2002

PI31 is a modulator of proteasome formation and antigen processing.

Regulation of the proteasome system, which is responsible for the generation of most MHC class I-bound peptides, occurs through the interaction of the 20S proteasome with several regulatory proteins. One of these is PI31, which acts in vitro as an inhibitor of proteasome activity. Here, we demonstrate that, rather than inhibiting proteasome function, PI31 acts as a selective modulator of the proteasome-mediated steps in MHC class I antigen processing. Overexpression of PI31 in mouse embryonic cells has no impact on proteasome-mediated proteolysis. Instead, PI31, which localizes at the nuclear envelope/endoplasmic reticulum membrane, selectively interferes with the maturation of immunoproteasome precursor complexes. Consequently, overexpression of PI31 abrogates MHC class I presentation of an immunoproteasome-dependent cytotoxic T lymphocyte epitope and reduces the surface MHC class I levels on IFN-gamma-treated mouse embryonic cells. Thus, PI31 represents a cellular regulator of proteasome formation and of proteasome-mediated antigen processing.

Adjuvants, Immunologic↗
PubMed1997

Oral feeding of renal tubular antigen abrogates interstitial nephritis and renal failure in Brown Norway rats.

We have examined whether oral feeding of antigen can regulate the expression of autoimmune interstitial nephritis induced by antigen-in-adjuvant (RTA/CFA) immunization of Brown Norway rats. Male rats were divided into six experimental groups: Group I, RTA/CFA immunization alone; Groups II, III, and IV were pretreated with 1 mg (Group II), 5 mg (Group III), and 25 mg (Group IV) of oral tubular antigen every other day for ten days, followed by RTA/CFA immunization; Group V was pretreated with a control antigen, followed by RTA/CFA immunization; and Group VI was immunized with CFA alone. Renal histology, inulin clearance, DTH responses to RTA, and IgG antibody responses to RTA were monitored as endpoints of the study. Our results demonstrated that Group III and IV animals had significantly less severe renal injury, as assessed by inulin clearance and extent of renal cortical involvement by mononuclear cells. Group II and IV animals had suppressed DTH responses, and only Group IV animals had significantly depressed antigen-specific IgG serum titers. Group III animals had neither suppressed DTH responses or IgG titers. We conclude that oral administration of tubular antigen can modulate the intensity of interstitial nephritis produced by immunization, but that the regulatory mechanism is not dependent (at all doses of fed antigen) on suppressed DTH reactivity to RTA or suppressed antigen-specific IgG.

Administration, Oral↗
PubMed2001

Expression of the type IV collagenase system during mouse kidney development and tubule segmentation.

Type IV collagenases matrix metalloproteinase-2 (MMP2) and MMP9 and their related proteins, MT1-MMP, tissue inhibitor of metalloproteinases 1 (TIMP1), TIMP2, and TIMP3, are expressed during kidney morphogenesis and nephrogenesis, but the renal ontogeny of these proteins is only partially known, and their persistence in the adult remains controversial. Their expression was analyzed from early metanephric stages to adulthood by Western blot semiquantitative analysis; laser confocal microscopy of whole-mount kidneys; and a two-step immunoperoxidase labeling procedure using specific markers of proximal tubule (megalin), ascending limb of Henle's loop (Tamm Horsfall protein), and collecting duct (Dolichos biflorus agglutinin lectin). By Western blot, all antigens were detected at day 11.5, peaked at day 16.5, and persisted in the adult at lower levels, although MMP2 was less modulated. All antigens were expressed in metanephric mesenchyme at embryonic day 11.5 and became concentrated in neural cell adhesion molecule-positive-induced mesenchymal cells at day 12.5. Only MT1-MMP and to a lesser extent MMP2 were detected in the ureter bud. At day 16.5, all antigens predominated in the cytoplasm of the proximal tubule, except TIMP1, which was mostly expressed in the ascending limb of Henle's loop and distal tubule. During tubule segmentation, components of the type IV collagenase system showed both spatial and temporal regulation. The distribution of gelatinases was not strictly superimposable to that of their natural inhibitors TIMP, especially for MMP9 and TIMP1. All components persisted in specific segments of the adult renal tubule, where MMP9, MMP2, and MT1-MMP showed an apical expression, suggesting that substrates for these enzymes should be in the tubule lumen or in the apical cell domain and not in the extracellular matrix. These results suggest that a regulated balance of gelatinase activity is required during kidney organogenesis and that gelatinases continue to play a role in adult renal tubule physiology.

Animals↗
PubMed2003

Human neutrophil chemotaxis is modulated by capsule and O antigen from an extraintestinal pathogenic Escherichia coli strain.

Gram-negative enteric bacilli, such as Escherichia coli, are common causes of nosocomial pneumonia. The interaction between pulmonary neutrophils and the infecting pathogen is a critical step in determining the outcome. Previous studies from our laboratory, for which a rat model of pneumonia was used, established that pulmonary neutrophil recruitment was modulated by the E. coli virulence factors capsule and O-specific antigen. To begin to understand the mechanism by which this recruitment occurs, we conducted in vitro and ex vivo chemotaxis assays, for which we used a clinically relevant E. coli isolate (CP9) and isogenic derivatives that were deficient in only the O antigen (CP921) or capsule (CP9.137) as chemoattractants with or without the high-affinity N-formylmethionyl-leucyl-phenylalanine receptor antagonist N-tert-butoxycarbonyl-methionine-leucine-phenylalanine (N-t-BOC). Given that only live E. coli was used for the initial in vitro chemotaxis assays, it was predicted that only N-t-BOC-sensitive chemotaxis would occur. However, both N-t-BOC-sensitive and -insensitive chemotaxis was observed. N-t-BOC-insensitive chemotaxis was mediated in part by interleukin 8, which was produced by neutrophils that had migrated toward E. coli. N-t-BOC-insensitive chemotaxis was only observed when live E. coli bacteria, not cell-free E. coli culture supernatants, were used as chemoattractants, suggesting that a direct E. coli-neutrophil interaction was necessary. The presence of both capsule and O antigen diminished total, N-t-BOC-sensitive, and N-t-BOC-insensitive neutrophil chemotaxis in vitro. The presence of capsule significantly decreased total, N-t-BOC-sensitive, and N-t-BOC-insensitive neutrophil chemotaxis ex vivo when cell-free bronchoalveolar lavage fluid from infected rats was used as the source of chemotactic factors. These effects of E. coli capsule and O antigen on neutrophil chemotaxis are novel, and they expand our understanding of the mechanisms by which these virulence traits contribute to the pathogenesis of gram-negative pneumonia and other extraintestinal infections.

Animals↗
PubMed1988

Chemically modified capsular polysaccharides as vaccines.

Capsular polysaccharides have assumed an important role as vaccines against disease caused by bacteria in humans. The concept of using pure definable polysaccharides devoid of their accompanying complex bacterial mass is technically elegant and is obviously capable of extension into other areas of immunoprophylaxis. However, problems have been identified which will need to be solved in order that the concept may be more widely adopted. Focusing on the meningococcal polysaccharides, possible solutions to two of these important problems, namely, the poor immunogenicity of the A and C polysaccharides in infants, and the poor immunogenicity of the B polysaccharide in all humans, are proposed. These solutions involve the use of a new generation of artificial synthetic antigens for modulating the immune response. For instance, conjugation of the A and C polysaccharides to tetanus toxoid converted them to T-cell dependent antigens in mice, thus making these conjugates potential infant vaccine candidates. Although a similar conjugation of the B polysaccharide failed to substantially enhance its immunogenicity in mice, this could be achieved by further chemical manipulation of the basic structure of the B polysaccharide. N-propionylation of the B polysaccharide, followed by its conjugation to tetanus toxoid, yielded an antigen, which when injected in mice, induced in them high titers of cross-reactive B polysaccharide-specific IgG antibodies. The chemical modification of polysaccharides requires an understanding of the interrelation between their structures and immunospecificities, and the structural elucidation of polysaccharides and the resultant monitoring of their structural modifications, can be conveniently accomplished using a wide range of NMR spectroscopic techniques. The capsular polysaccharides of many of the bacteria which cause meningitis in humans contain sialic acid and have extensive structural homology with human tissue. As a result of this homology the immunospecificities of these polysaccharides are complex, being based on unconventional conformational determinants.

Antibodies, Bacterial↗
PubMed2005

Immunization with the gene expressing woodchuck hepatitis virus nucleocapsid protein fused to cytotoxic-T-lymphocyte-associated antigen 4 leads to enhanced specific immune responses in mice and woodchucks.

A number of options are available to modify and improve DNA vaccines. An interesting approach to improve DNA vaccines is to fuse bioactive domains, like cytotoxic-T-lymphocyte-associated protein 4 (CTLA-4), to an antigen. Such fusion antigens are expressed in vivo and directed to immune cells by the specific bioactive domain and therefore possess great potential to induce and modulate antigen-specific immune responses. In the present study, we tested this new approach for immunomodulation against hepadnavirus infection in the woodchuck model. Plasmids expressing the nucleocapsid protein (WHcAg) and e antigen (WHeAg) of woodchuck hepatitis virus (WHV) alone or in fusion to the extracellular domain of woodchuck CTLA-4 and CD28 were constructed. Immunizations of mice with plasmids expressing WHcAg or WHeAg led to a specific immunoglobulin G2a (IgG2a)-dominant antibody response. In contrast, fusions of WHcAg to CTLA-4 and CD28 induced a specific antibody response with comparable levels of IgG1 and IgG2a. Furthermore, the specific IgG1 response to WHcAg/WHeAg developed immediately after a single immunization with the CTLA-4-WHcAg fusion. Woodchucks were immunized with plasmids expressing WHeAg or the CTLA-4-WHcAg fusion and subsequently challenged with WHV. CTLA-4-WHcAg showed an improved efficacy in induction of protective immune responses to WHV. In particular, the anti-WHsAg antibody response developed earlier after challenge in woodchucks that received immunizations with CTLA-4-WHcAg, consistent with the hypothesis that anti-WHs response is dependent on a Th cell response to WHcAg. In conclusion, the use of fusion genes represents a generally applicable strategy to improve DNA vaccination.

Animals↗
PubMed1989

HLA class II antigens: structure, function, and expression in immunodeficiencies, autoimmune diseases, and allograft rejection.

The major histocompatibility complex (MHC) genes, coding for the histocompatibility leukocyte antigens (HLAs) are located on the short arm of chromosome 6. The HLA gene products are involved in many immune responses. Class I and class II molecules are composed of two subunits. Class I antigens are expressed on all cell types except red blood cells; class II molecules have a more limited distribution and are found only on certain cell types. A review of our current knowledge of the genes coding for these molecules, their biochemical analysis, and the current investigation into the three-dimensional structure of the glycoproteins will allow us to understand better how this complex system, which has been preserved in animal species throughout the evolutionary process, operates. The biologic significance of HLA class I and class II molecules in the development of an efficient immune system that permits our survival in the sea of microorganisms in which we are immersed is illustrated by the severe and lethal infections that occur when these antigens are absent. Important and interesting variations in class II antigen expression are also observed in certain autoimmune diseases. Furthermore, the role of these antigens in the allogeneic reaction of graft rejection has now been clearly identified. It has become increasingly apparent how important it is to understand the antigenic variation between organs, or even between cells within an organ, and to be able to identify the circumstances that are associated with modulation of antigen expression.

Autoimmune Diseases↗
PubMed2001

Selective immunointervention in autoimmune diseases: lessons from multiple sclerosis.

Activation of peripheral T cells by foreign and self antigens is under stringent control by different mechanisms, both thymic and peripheral. Control of T cell reactivity is accomplished by three major types of mechanisms: 1) deletion, the physical elimination of T cells specific for a given antigen, 2) anergy, the functional incapacity of T cells to respond to antigen, 3) suppression, the inhibition of T cell function by a regulatory (suppressor) cell. Their failure may lead to autoimmune diseases. The progress in understanding T cell activation, inactivation and modulation is being translated into strategies able to induce selective immunosuppression to treat different pathological situations, notably autoimmune diseases, allergies, and allograft rejection. The medical need for selective immunosuppression is very high, as the available immunosuppressive drugs are substantially inadequate because of limited efficacy, modest selectivity, and considerable toxicity. Key attack points for selective immunointervention have been identified: modulation of antigen recognition, co-stimulation blockade, induction of regulatory cells, deviation to non-pathogenic or protective responses, neutralization of proinflammatory cytokines, induction or administration of anti-inflammatory cytokines, and modulation of leukocyte trafficking. All these forms of immunointervention have been successfully used to prevent and sometimes treat experimental autoimmune diseases. Based on these results, expectations have been raised for exploiting the same strategies to inhibit the activation of human autoreactive T cells. In this overview, we will examine recent advances towards immunointervention in multiple sclerosis (MS) as a paradigm for successes and failures of current immunotherapeutic approaches in human autoimmune diseases.

Administration, Oral↗
PubMed2000

The SH2 domain containing tyrosine phosphatase-1 down-regulates activation of Lyn and Lyn-induced tyrosine phosphorylation of the CD19 receptor in B cells.

SHP-1 is a cytosolic tyrosine phosphatase implicated in down-regulation of B cell antigen receptor signaling. SHP-1 effects on the antigen receptor reflect its capacity to dephosphorylate this receptor as well as several inhibitory comodulators. In view of our observation that antigen receptor-induced CD19 tyrosine phosphorylation is constitutively increased in B cells from SHP-l-deficient motheaten mice, we investigated the possibility that CD19, a positive modulator of antigen receptor signaling, represents another substrate for SHP-1. However, analysis of CD19 coimmunoprecipitable tyrosine phosphatase activity in CD19 immunoprecipitates from SHP-1-deficient and wild-type B cells revealed that SHP-1 accounts for only a minor portion of CD19-associated tyrosine phosphatase activity. As CD19 tyrosine phosphorylation is modulated by the Lyn protein-tyrosine kinase, Lyn activity was evaluated in wild-type and motheaten B cells. The results revealed both Lyn as well as CD19-associated Lyn kinase activity to be constitutively and inducibly increased in SHP-1-deficient compared with wild-type B cells. The data also demonstrated SHP-1 to be associated with Lyn in stimulated but not in resting B cells and indicated this interaction to be mediated via Lyn binding to the SHP-1 N-terminal SH2 domain. These findings, together with cyanogen bromide cleavage data revealing that SHP-1 dephosphorylates the Lyn autophosphorylation site, identify Lyn deactivation/dephosphorylation as a likely mechanism whereby SHP-1 exerts its influence on CD19 tyrosine phosphorylation and, by extension, its inhibitory effect on B cell antigen receptor signaling.

Animals↗
PubMed1998

T-cell activation in autoimmune and inflammatory diseases.

Recent progress in experimental models and human genetic linkage studies have provided new insight into the pathogenesis of autoimmunity. Both antigen-specific and antigen-nonspecific signals are crucial in the development of autoimmune disease. Interestingly, several of the single gene loci that have been identified as potential causes of autoimmune disease encode molecules that regulate antigen-nonspecific modulation of immunity. The focus of this review is the role of the opposing signals transduced by the CD28 and cytotoxic T-lymphocyte antigen-4 receptors that bind the B7 costimulatory ligands. Recent studies suggest that CD28 signals activate T cells, whereas cytotoxic T-lymphocyte antigen-4 signals deactivate T cells. importantly, both signals contribute to the induction of autoimmunity and offer novel targets for future therapeutic strategies to treat autoimmune disease.

Abatacept↗
PubMed2002

Simian virus 40 large T antigen and two independent T-antigen segments sensitize cells to apoptosis following genotoxic damage.

The simian virus 40 (SV40) large tumor (T) antigen is sufficient to transform cells in cultures and induce tumors in experimental animals. Transformation of primary cells in cultures requires both overcoming growth arrest by stimulating the cell cycle and blocking cell death activities presumably activated by oncogene-mediated hyperproliferation signals. The study presented here examined the ability of specific regions and activities of T antigen to modulate apoptosis in cells treated with the genotoxic agent 5-fluorouracil (5-FU). The results showed that the expression of full-length T antigen rendered rat embryo fibroblasts (REF) sensitive to 5-FU-induced apoptosis. Thus, neither the p53-binding region nor the Bcl-2 homology region of T antigen was sufficient to prevent cell death induced by the DNA-damaging agent. T-antigen-mediated sensitization occurred independently of retinoblastoma protein or p53 and p300 binding. An N-terminal segment containing the first 127 T-antigen amino acids (T1-127) was sufficient to sensitize cells. A C-terminal segment consisting of T-antigen amino acids 251 to 708 (T251-708) also sensitized cells to 5-FU-induced apoptosis. This sensitization did not occur when T251-708 was targeted to the nucleus by inclusion of the SV40 nuclear localization signal. The introduction of mutations into the T-antigen J domain resulted in mutation-specific and variable inhibition of apoptosis. This result suggested that either the structural or the functional integrity of the J domain is required to sensitize cells to apoptosis. Treatment of REF or REF expressing full-length T antigen, an N-terminal segment, or T251-708 resulted in increased expression of the p53-responsive MDM2 gene; apoptosis occurred through a p53-dependent pathway, as p53-null cells expressing these T antigens were resistant to 5-FU-induced apoptosis. Possible mechanisms involved in sensitizing cells to a p53-dependent apoptosis pathway in spite of the ability of T antigen to bind and inactivate the transcriptional transactivating activity of p53 are discussed.

Animals↗
PubMed1975

Somatic hybrid of thymus leukemia (.

A somatic hybrid of ASL-1 leukemia cells [H-2a, thymus leukemia (TL)1,2,3, Thy-1b] and LM(TK)-cells [H-2-k, TL(-), Thy-1 (-), thymidine kinase deficient] was formed with the aid of inactivated Sendai virus. The selection of hybrid cell clones was facilitated by the inability of ASL-1 cells to grow in vitro and of LM(TK)-cells to survive in hypoxanthine/amethopterin/thymidine medium. The H-2 antigens of both parental cells were formed in approximately equivalent amounts by the hybrid cells, and they possessed a hybrid karyotype. As determined by five independent experimental procedures (antibody and complement-mediated cytotoxicity tests, the reduction of specific antibody activity of antiserum of known titer, immunofluorescent tests, mixed hemagglutination tests, and their direct isolation), TL antigens but not Thy-1 antigens were formed by the hybrid cells. TL antigens of the hybrids failed to undergo modulation under conditions leading to the modulation of TL antigens of parental ASL-1 cells. Modulation was attempted with TL 1,3, TL 2, or TL 1,2,3 antisera of high titer. thybrid cells were incubated for up to 30 hr in medium with TL antisera. Both direct and indirect immune methods were attempted. These results indicate that cellular mechanisms controlling the expression of TL antigens may be distinguished from the capacity of the cells to undergo modulation.

Animals↗