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Biomedical subjects

M Shenoy

Publications and source records attributed to M Shenoy.

31 records · Page 2Linked to original sources
PubMed1993

Suppression of experimental autoimmune myasthenia gravis by epitope-specific neonatal tolerance to synthetic region alpha 146-162 of acetylcholine receptor.

A gene conversion event between Ebb and Abb in the B6.C-H-2bm12 (bm12) strain, which alters three amino acids in the C-terminal half of the first domain of Abb (Ile-67-->Phe; Arg-70-->Gln; Thr-71-->Lys) resulted in resistance to experimental autoimmune myasthenia gravis (EAMG) pathogenesis. To study the effect of bm12 mutation on the T-cell responses to epitopes of acetylcholine receptor (AChR)-alpha subunit, C57BL6 (B6) and bm12 mice were primed with Torpedo californica AChR, and the profiles of T-lymphocyte proliferation were determined with 18 synthetic overlapping peptides encompassing the entire extracellular portion of the AChR-alpha subunit. The proliferative responses of AChR-primed bm12 lymphocytes were markedly reduced to two (alpha 146-162 and alpha 182-198) of the three AChR peptides (alpha 111-126, alpha 146-162, and alpha 182-198) that are immunodominant in B6 mice. Thus, the Ab residues encompassing the region 67-71 determine the immunogenicity of two of the AChR-alpha subunit T-cell epitopes. To test the involvement of AChR-alpha chain epitopes within peptide alpha 146-162 in EAMG pathogenesis, B6 mice were neonatally tolerized with soluble peptide alpha 146-162, and subsequently immunized with AChR in complete Freund's adjuvant. Neonatal tolerance to AChR or to peptide alpha 146-162 reduced the incidence of clinical myasthenia gravis and suppressed serum anti-AChR antibodies. This indicates the involvement of T-cell epitopes within AChR-alpha subunit region alpha 146-162 in EAMG pathogenesis. Neonatal tolerance to peptide alpha 146-162 could have caused specific clonal deletion, and/or clonal anergy, and/or recruited suppressor cells to prevent clinical EAMG. Presumably, epitope(s) with AChR alpha 146-162, in the context of Ab encompassing region 67-71, stimulate specific T helper cells which interact with specific B cells to produce pathogenic antibodies, the primary culprit causing the end plate lesion in patients with myasthenia gravis.

Amino Acid Sequence↗
PubMed1993

Induction of experimental autoimmune myasthenia gravis with acetylcholine receptors using a nonionic block copolymer as adjuvant.

To induce autoimmune diseases in animals, the auto-antigen has to be emulsified in adjuvants (e.g., complete Freund's adjuvant) containing microbial products such as Mycobacterium tuberculosis. But these powerful immunoadjuvants are not without undesirable immune response to the microbial proteins and induction of adjuvant arthritis, which could interfere with the antigen specific autoimmune response to be tested. This study was performed to evaluate the requirement of microbial products in the induction of experimental autoimmune diseases, and to identify an adjuvant without unwanted immune responses. C57BL/6 mice were inoculated with Torpedo acetylcholine receptors (T-AChR) emulsified in Titermax (TM), an adjuvant containing nonionic block copolymer and no microbial products, and evaluated for experimental autoimmune myasthenia gravis (EAMG) susceptibility. Mice immunized with T-AChR in TM demonstrated characteristic myasthenic muscle weakness with electrophysiological defect, elevated serum anti-AChR antibodies, and muscle AChR loss. None of the mice that received TM alone had muscle weakness, serum anti-AChR antibodies or muscle AChR loss. The data imply that microbial products are not critical in the induction of autoimmune diseases like myasthenia gravis in mice. Further, nonionic block copolymer could be an ideal adjuvant in the induction of autoimmune diseases in animals.

Adjuvants, Immunologic↗
PubMed1992

Suramin inhibits the mixed lymphocyte reaction by suppressing lymphokine production.

New compounds with a greater potency than cyclosporin A (CyA) for thwarting host rejection of organ transplantation are being sought. Suramin sodium may be a novel drug to prevent or delay graft rejection and graft-vs-host disease (GVHD), because of its in vitro and in vivo immunosuppressive properties. Since the allogeneic mixed lymphocyte reaction (MLR) is considered to be the in vitro counterpart of the initial T-lymphocyte recognition and response to allogeneic histocompatibility antigens on grafted tissue or organ and to GVHD, we initially evaluated the in vitro suppressive effect of suramin in the allogeneic MLR. Suramin inhibited the H-2- and HLA-incompatible MLR in a dose-dependent manner. The suppressive effect was observed both in the primary and in the secondary MLR. The suppression of the MLR by suramin is due predominantly to the inhibition of interleukin-2 (IL-2) production by the responding T cells.

Animals↗
PubMed1991

In vivo administration of TNF-alpha prevents EMC-M virus induced viral encephalitis.

EMC-M virus causes a monophasic paralytic syndrome characterized by encephalitic lesions in the brain and patchy demyelinating lesions in the spinal cord and nerve roots of BALB/c mice. Since the replication of EMC virus in vitro is inhibited by tumor necrosis factor (TNF)-alpha we have studied the effect of in vivo administration of this cytokine on the acute disease. Our studies show that periodic administration of TNF-alpha to animals infected with EMC-M reduces viral titers in the brain, and decreases the degree of clinical paralysis and the severity of the inflammatory lesions in the brain.

Animals↗
PubMed1991

Indirect role of T cells in development of polioencephalitis and encephalomyelitis induced by encephalomyocarditis virus.

Infection of female BALB/c mice with encephalomyocarditis virus results in the development of a paralytic syndrome in 7 to 10 days postinoculation. Previous studies had suggested the involvement of an immune component in the development of central nervous system pathology. We have examined the effects of T-cell depletion on the development of polioencephalitis (neuronal necrosis and inflammation of the brain and brain stem) and the relative contribution of the CD4+ and CD8+ subsets following the establishment of viremia. We show that monoclonal antibody depletion of T cells is effective in the reduction of polioencephalitis when given prior to viral inoculation. However, administration of the antibodies 12 h or more after viral inoculation failed to alter the development of polioencephalitis or encephalomyelitis. We conclude that T cells are involved in the development of central nervous system disease during the initial stages of infection but are not responsible for the later progression of disease.

Animals↗
PubMed1990

Ek alpha transgene in B10 mice suppresses the development of myasthenia gravis.

Mice bearing the H-2b haplotype are susceptible to the development of experimental autoimmune myasthenia gravis (EAMG), induced by acetylcholine receptor (AChR) autoimmunity. One of the genes influencing EAMG susceptibility has been mapped to the Ab locus of the major histocompatibility complex, and the A beta chain has been implicated in the pathogenesis. Mice of the H-2b haplotype, including C57BL/10 (B10), have a genomic deletion of the E alpha gene and therefore fail to express the E molecule on their cell surface. To test the hypothesis that failure to express the cell surface E molecule in B10 mice contributes to EAMG pathogenesis, Ek alpha transgenic B10 mice expressing the E molecule were examined. Expression of the E molecule in Ek alpha transgenic B10 mice partially prevented the development of EAMG.

Animals↗
PubMed1986

Immune response gene control of lymphocyte proliferation induced by acetylcholine receptor-specific helper factor derived from lymphocytes of myasthenic mice.

The role of lymphokines secreted by acetylcholine receptor (AChR)-reactive lymphocytes in the regulation of an autoimmune response to AChR has not been studied in the human or murine model of myasthenia gravis. We investigated whether AChR-immune lymphocytes derived from mice with experimental autoimmune myasthenia gravis (EAMG) can produce an AChR-specific, genetically controlled soluble factor with biologic activity. AChR-reactive lymphocytes of mice with EAMG secreted an AChR-specific helper factor in vitro, which induced proliferation of AChR-immune but not Mycobacterium tuberculosis-immune lymphocytes. Recombinant, I-A mutant, and monoclonal anti-I-A antibody analyses suggest that AChR-specific helper factor-induced lymphocyte proliferation is controlled by an immune response gene at the I-A subregion of the murine major histocompatibility complex, and is mediated by the I-A molecule.

Animals↗
PubMed1983

Haptoglobulin phenotypes in leprosy.

Haptoglobulin phenotyping was carried out in fifty controls and in thirty five leprosy patients. In controls the incidence Hp phenotypes 2-2, 2-1 and 2-1 (Mod) is 76%, 16% and 8% respectively. In leprosy patients, the incidence of phenotypes 2-2, 2-1, 1-1 and 0-0 is 77%, 11%, 3% and 9% respectively. The incidence of phenotype 2-2, 1-1 and 0-0 is more in leprosy patients than in controls and is significant (p less than 0.05). In none of the leprosy patients phenotype 2-1 (Mod) was recorded.

Haptoglobins↗