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Biomedical subjects

M H Sayegh

Publications and source records attributed to M H Sayegh.

At least 181 records · Page 10Linked to original sources
PubMed1990

HLA class II-restricted binding of muramyl peptides to B lymphocytes of normal and narcoleptic subjects.

The propensity for narcolepsy, a clinical sleep disorder of unknown etiology, is virtually totally included within the HLA-DR2,DQw1 (DRw15,DQw6) phenotype. The disorder is characterized by decreased sleep latency, early onset of rapid eye movement sleep, and a paucity of nocturnal slow-wave sleep. Muramyl peptides, naturally occurring bacterial cell wall peptidoglycans, potently enhance the duration and amplitude of slow-wave sleep in animals, bind to murine mononuclear cells, and exhibit a major histocompatibility complex-restricted immunoadjuvant effect in mice. We examined the binding of muramyl peptides to peripheral blood mononuclear leukocytes of HLA-typed normal (n = 13) and narcoleptic (n = 10) subjects. Muramyl peptides bound specifically and with high affinity to normal B- but not T-lymphocyte-enriched preparations. There was no significant specific binding to B-cell-enriched preparations from narcoleptic patients. Furthermore, B-lymphocyte-enriched preparations of normal individuals who had the HLA-DR2,DQw1 phenotype (n = 8) exhibited a lower level of specific binding than those of normals who did not have this phenotype (n = 5, p less than 0.001). These observations are an additional indication of the relevance of muramyl peptides to slow-wave sleep and provide a basis for a better understanding of the relation between narcolepsy and the MHC at the biochemical level.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1989

Mixed lymphocyte response-generated suppressor cell specificity in humans is major histocompatibility complex-restricted.

To formally test the hypothesis that allospecificity of the human mixed lymphocyte response-generated suppressor cells is restricted to the major histocompatibility complex, 18 primary mixed lymphocyte responses, using peripheral blood lymphocytes of 10 HLA-typed families, were used to generate suppressor effector cells. Responder lymphocytes shared one HLA haplotype with the stimulator cells. At day 10, the effector cells were tested for their ability to suppress proliferation of 55 test mixed lymphocyte responses consisting of naive autologous lymphocytes as responders and irradiated cells from individual family members as stimulators. Suppression was predicted when the test culture stimulators expressed the same HLA haplotype to which the suppressor cells were primed. There was statistically significant correlation between suppression and HLA haplotype sharing (p = 0.0143). In 6 out of 13 assays, however, we observed suppression that was not predicted on the basis of relevant HLA haplotype sharing. These stimulators shared only HLA-A2 with the priming haplotype. HLA antigen sharing was not seen in the 7 remaining, nonsuppressed cultures. We conclude that, within families, the effector function of in vitro generated suppressor cells is restricted by the major histocompatibility complex.

Haplotypes↗
PubMed1989

Anti-CD4 monoclonal antibody effects cellular hyporesponsiveness and prolongs renal allograft survival in the rat.

LEW strain rats received BN strain renal allografts and were treated with daily injections of 100 micrograms BWH-4, a new IgG2a mouse anti-rat CD4 monoclonal antibody, intravenously for 5 to 10 days. These animals had a median actuarial survival of 28 days. Control animals rejected their grafts and died of uremia between day 6 and 8 post transplant. Animals treated with BWH-4 did not suffer acute graft loss and had stable renal function throughout the follow-up period of 5 weeks. Peripheral blood, lymph node, and splenic lymphocytes showed 60-80% decrease in the CD4+ subset which normalized by 4 weeks after transplantation. There was depressed proliferative response of lymph node cells to alloantigen and mitogen which persisted up to 4 weeks after cessation of therapy. Treated animals produced anti-BN antibodies as well as antibodies to the infused BWH-4. There was no correlation, however, between these humoral responses and allograft function. We conclude that low-dose monotherapy with the BWH-4 anti-CD4 monoclonal antibody effects cellular hyporesponsiveness, prevents acute renal allograft rejection, and prolongs survival.

Animals↗
PubMed1989

Requirements for the induction of allospecific CD8+ suppressor T cells in the rat primary mixed lymphocyte response. CD4+, CD45R+ T cells, or supernatant factor.

We examined the requirements for the induction of the MLR-generated allospecific CD8+ suppressor T cells in the rat. Depleting the responder population of CD4+ T cells before initiating the primary MLR abrogates the generation of day-5 CD8+ T suppressor effectors. Readdition of at least 10% CD4+ T cells to the CD4+ depleted primary MLR reconstitutes suppressor cell generation. Using the anti-CD45R monoclonal antibody OX22, we also show that the T suppressor inducer cells are CD4+ CD45R+. Using a dual chamber Transwell culture system, which allows cells to be co-incubated without direct cell-to-cell contact, we show that a soluble factor/s, produced during the course of the primary MLR, is capable of inducing naive CD8+ T cells to become suppressor effectors but only when these CD8 T cells are in direct contact with allogeneic stimulators. Allospecificity is conferred by the stimulator cells and not by the suppressor-inducer factor. The supernatant of day-5 primary MLR is also capable of inducing antigen-specific suppressor effectors from naive CD8+ T cells, and also only in the presence of allogeneic stimulator cells. Recombinant human IL-2, in doses that are up to five times the amount present in the supernatant cultures, is unable to induce suppressor-effector cells from naive CD8+ T cells. We conclude that, to become allospecific suppressor effectors, naive CD8+ T cells require contact with allogeneic stimulator cells and either CD4+ CD45R+ suppressor inducer cells or suppressor inducer factor/s produced during the course of the primary MLR.

Animals↗