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Induction of suppressor cell activity by concanavalin a (Con A) in the absence of DNA synthesis
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Annual American Association for Clinical Histocompatibility Testing Meeting, 1980 responders. In families in which the disease appears to segregate with a certain haplotype, irradiated T cells from affected as well as from nonaffected members who share the respective haplotype, display the capacity of inhibiting MLC reactivity by 60% or more. Monocytes, B cells or sera from these individuals have no MLC suppressor activity. The presence of suppressor T cell activity was confirmed on repeat bleedings from the same individuals, yet could only be demonstrated when fresh rather than frozen -i~phocytes were tested. No individual with MLC suppressor activity was found in the spinocerebellar ataxia family in which the disease segregated independently of HLA. Although MLC suppressor T cells were detected in individuals ~,ith a variety of other conditions, family studies failed to reveal any segregation pattern. The observations suggest the possible involvement of an immunologic mechanism in the etiopathogeny of the HLA-linked form of spinocerebellar ataxia.
INDUCTION OF SUPPRESSOR CELL ACTIVITY BY CONCANAVALIN A (CON A) IN THE ABSENCE OF DNA SYNTHESIS. M. Suthanthiran, O.S. Won, A.L. Rubi n, A. Novo@rodsk~, and K.H.._ Stenzel. Rogosin Kidney Center, The New York Hospital-Cornell Univ. Med. Ctr., New York, N.Y. The differentiation of lymphoid cells is thought to be dependent upon DNA synthesis and cellular proliferation. The generation of helper, suppressor, and cytotoxic T-lymphocytes (CTL) has, however, been accomplished in the absence of DNA synthesis in murine systems. We now report that human peripheral blood lymphocytes (PBL) can be triggered by Con A to suppress the generation of primary (ie ) CTL in the absence of DNA synthesis. Primary CTL were generated in an unidirectional mixed lymphocyte culture (MLC~. PBL syngeneic to responder in MLC were exposed to 45 ug/ml Con A (Con A primed cells) or to PBS (control cells) and then added to the MLCs at the time of initiation of the cultures. Three different Con A treatment protocols were used; exposure to Con A for 20 mins, 24 hrs, and 48 hrs. Con A primed cells (duration of exposure to Con A, 24 hrs and 48 hrs) suppressed the generation of 1 CTL, as previously described. More importantly, PBL exposed to Con A for only 20 mins and irradiated to prevent DNA synthesis, significantly suppressed 1 CTL generation. In 6 allogeneic combinations, the % specific chromium release (SCR) was 27 + 8% (mean~SEM) when effector cells were responders in MLCs that were co-cultured with irradiated and untreated cells and 8+3% with effector cells that were co-cultured with irradiated and Con A exposed (20 mins) cells (p <.01). Our data indicate that, human PBL can be induced to acquire suppressor cell activity even in the absence of DNA synthesis.
Annual American Association for Clinical Histocompatibility Testing Meeting, 1980 responders. In families in which the disease appears to segregate with a certain haplotype, irradiated T cells from affected as well as from nonaffected members who share the respective haplotype, display the capacity of inhibiting MLC reactivity by 60% or more. Monocytes, B cells or sera from these individuals have no MLC suppressor activity. The presence of suppressor T cell activity was confirmed on repeat bleedings from the same individuals, yet could only be demonstrated when fresh rather than frozen -i~phocytes were tested. No individual with MLC suppressor activity was found in the spinocerebellar ataxia family in which the disease segregated independently of HLA. Although MLC suppressor T cells were detected in individuals ~,ith a variety of other conditions, family studies failed to reveal any segregation pattern. The observations suggest the possible involvement of an immunologic mechanism in the etiopathogeny of the HLA-linked form of spinocerebellar ataxia.
INDUCTION OF SUPPRESSOR CELL ACTIVITY BY CONCANAVALIN A (CON A) IN THE ABSENCE OF DNA SYNTHESIS. M. Suthanthiran, O.S. Won, A.L. Rubi n, A. Novo@rodsk~, and K.H.._ Stenzel. Rogosin Kidney Center, The New York Hospital-Cornell Univ. Med. Ctr., New York, N.Y. The differentiation of lymphoid cells is thought to be dependent upon DNA synthesis and cellular proliferation. The generation of helper, suppressor, and cytotoxic T-lymphocytes (CTL) has, however, been accomplished in the absence of DNA synthesis in murine systems. We now report that human peripheral blood lymphocytes (PBL) can be triggered by Con A to suppress the generation of primary (ie ) CTL in the absence of DNA synthesis. Primary CTL were generated in an unidirectional mixed lymphocyte culture (MLC~. PBL syngeneic to responder in MLC were exposed to 45 ug/ml Con A (Con A primed cells) or to PBS (control cells) and then added to the MLCs at the time of initiation of the cultures. Three different Con A treatment protocols were used; exposure to Con A for 20 mins, 24 hrs, and 48 hrs. Con A primed cells (duration of exposure to Con A, 24 hrs and 48 hrs) suppressed the generation of 1 CTL, as previously described. More importantly, PBL exposed to Con A for only 20 mins and irradiated to prevent DNA synthesis, significantly suppressed 1 CTL generation. In 6 allogeneic combinations, the % specific chromium release (SCR) was 27 + 8% (mean~SEM) when effector cells were responders in MLCs that were co-cultured with irradiated and untreated cells and 8+3% with effector cells that were co-cultured with irradiated and Con A exposed (20 mins) cells (p <.01). Our data indicate that, human PBL can be induced to acquire suppressor cell activity even in the absence of DNA synthesis.