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Regulation of immunoglobuklin production in bone marrow transplant recepients
22
Abstracts
USING MIXED LYMPHOCYTE CULTURE REACTIVITY TO PREDICT OUTCOME OF IN UTERQ BONE MARROW TRANSPLANTATION. D.Y. Muirhead, T. J. Kuehl, J. L. VandeBerg, E. M. Menchaca, M.P. Downs and G. D. Roodman, Department of Surgery, University of Texas Health Science Center at San Antonio Texas. In utero bone marrow transplantation offers many advantages for the cure of some genetic disorders. In our study the cellular immune reactivity of baboon fetuses (Papio sp.) was tested in mixed lymphocyte culture (MLC). Fetuses were tested against their mothers, against an unrelated pool, and in the case of fetuses given unrelated bone marrow transplants in utero, against their specific bone marrow donors. Fetal baboons as young as 80 days (182 day normal gestation) responded to maternal and unrelated allogeneic lymphocytes. Six fetuses were transplanted with bone marrow from unrelated and unmatched adult baboons. Three of six fetuses engrafted at low levels (demonstrated by GPI chimerism), but the grafts were lost by term. These fetuses reacted more strongly to their donors than to a pool of unrelated controls in MLC tests run post-transplantation, perhaps suggesting sensitization to alloantigens of the donor. Our data demonstrate that fetal lymphocytes are immunologically competent in MLC's which may allow selection of appropriate donor-recipient combinations for in utero bone marrow transplantation.
REGULATION OF IMMUNOGLOBULIN PRODUCTION IN BONE MARROWTRANSPLANT RECIPIENTS. ~[M Gebel and RA Bray, Rush Medical Center, Chicago, IL Bone marrow transplant (BMT) recipients suffer from a severe combined immunodeflciency, placing them at high risk for life threatening infections. Several investigators suggest that suppresor cells which emerge post-transplant down regulate the immune system and are responsible for the immunodeficlency. In BMT recipients, 2070% of their circulating lymphocytes co-express CD8 and CDIIb (normal-5-15%). These CD8/IIh cells contain two subpopulatlons distinguished by their expression of CD3: CD3 + CD8/IIb suppressor T (Ts) cells and CD3- CD8/IIb natural killer (NK) cells which express CDI6. Both T s and NK cells have in vitro immunoregulatory activity and may also be active In vivo. We analyzed serum levels of IgA and IgM in 18 patients wlth >25% CD8/IIb cells. IgM and IgA were <10% of normal in 7/7 patients whose CD8/IIb cells were T s lymphocytes. Among Ii subjects whose CD8/IIb cells were NK cells, 5 had severely depressed and 6 had normal levels of IgM and IgA. CD57 was not expressed on NK cells from those patients with reduced IgM and IgA but was present on >60% of the NK cells from patients with normal levels of IgM and IgA. In summary, there are at least 3 distinct regulatory subsets of CD8/IIb lymphocyte populations in BMT recipients: I)T s cells; 2)CD57+NK cells and 3)CD57- NK cells. Our data support the hypothesis that CD8/IIb subsets differentially regulate IgM and IgA production in vlvo. Potentially, such information may Identify those BMT recipients at higher risk for infection.
Abstracts
USING MIXED LYMPHOCYTE CULTURE REACTIVITY TO PREDICT OUTCOME OF IN UTERQ BONE MARROW TRANSPLANTATION. D.Y. Muirhead, T. J. Kuehl, J. L. VandeBerg, E. M. Menchaca, M.P. Downs and G. D. Roodman, Department of Surgery, University of Texas Health Science Center at San Antonio Texas. In utero bone marrow transplantation offers many advantages for the cure of some genetic disorders. In our study the cellular immune reactivity of baboon fetuses (Papio sp.) was tested in mixed lymphocyte culture (MLC). Fetuses were tested against their mothers, against an unrelated pool, and in the case of fetuses given unrelated bone marrow transplants in utero, against their specific bone marrow donors. Fetal baboons as young as 80 days (182 day normal gestation) responded to maternal and unrelated allogeneic lymphocytes. Six fetuses were transplanted with bone marrow from unrelated and unmatched adult baboons. Three of six fetuses engrafted at low levels (demonstrated by GPI chimerism), but the grafts were lost by term. These fetuses reacted more strongly to their donors than to a pool of unrelated controls in MLC tests run post-transplantation, perhaps suggesting sensitization to alloantigens of the donor. Our data demonstrate that fetal lymphocytes are immunologically competent in MLC's which may allow selection of appropriate donor-recipient combinations for in utero bone marrow transplantation.
REGULATION OF IMMUNOGLOBULIN PRODUCTION IN BONE MARROWTRANSPLANT RECIPIENTS. ~[M Gebel and RA Bray, Rush Medical Center, Chicago, IL Bone marrow transplant (BMT) recipients suffer from a severe combined immunodeflciency, placing them at high risk for life threatening infections. Several investigators suggest that suppresor cells which emerge post-transplant down regulate the immune system and are responsible for the immunodeficlency. In BMT recipients, 2070% of their circulating lymphocytes co-express CD8 and CDIIb (normal-5-15%). These CD8/IIh cells contain two subpopulatlons distinguished by their expression of CD3: CD3 + CD8/IIb suppressor T (Ts) cells and CD3- CD8/IIb natural killer (NK) cells which express CDI6. Both T s and NK cells have in vitro immunoregulatory activity and may also be active In vivo. We analyzed serum levels of IgA and IgM in 18 patients wlth >25% CD8/IIb cells. IgM and IgA were <10% of normal in 7/7 patients whose CD8/IIb cells were T s lymphocytes. Among Ii subjects whose CD8/IIb cells were NK cells, 5 had severely depressed and 6 had normal levels of IgM and IgA. CD57 was not expressed on NK cells from those patients with reduced IgM and IgA but was present on >60% of the NK cells from patients with normal levels of IgM and IgA. In summary, there are at least 3 distinct regulatory subsets of CD8/IIb lymphocyte populations in BMT recipients: I)T s cells; 2)CD57+NK cells and 3)CD57- NK cells. Our data support the hypothesis that CD8/IIb subsets differentially regulate IgM and IgA production in vlvo. Potentially, such information may Identify those BMT recipients at higher risk for infection.