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Antibodies elution study from failed liver allografts
Absu'acts
II1
#328 8.4
ANTIBODIES ELUTION STUDY FROM FAILED LIVER ALLOGRAFTS A Yagihashi, K Tanaka, K Noguchi, M Kobayashi, M Vanek, A Konno, T Takenaka, Y ¥oshida, TE Starzl and ¥ lwaki. University of Pittsburgh Tissue Typing I~beratory, Pittsburgh, PA. The deleterious effect of a positive T lymphocyte crossmatch in liver transplantation has b e e n demonstrated. In order to characterize the antibody deposited t o t he failed grafts, we further analized the acid eluates from the 30 failed liver a11ografts (20 patients with primary liver allograft and I0 with 2nd or more). There were 8 recipients transplanted across positive T cell orossmatches (5 in primary and 3 in regrafts) using DTT treated sera. T lymphocytotoxic reactivities w e r e demonstrated in 9 eluates from the p r i m a r y a l l o g r a f t s and in 3 from the regrafts, which was not influenced by the presence of preformed antibodies. Although only one eluate showed the specificity against the missmatched HI& antigens, the HLA specificities were n o t assigned in the remaining eluates. ~n addition, 3 eluates revealed platelet specific reaotivities. In conclusion, some other transplantation antigens besides H L A m i g h t be involved in liver allograft failure.
#329 8.7
EFFECTS OF IMMUNOSUPPRESSIVE MACROLIDES AND NUCLEOT1DE SYNTHETASE INHIBITORS ON PROLIFERATION OF LYMPHOID CELLS INDUCED VIA DISTINCT SIGNAL TRANSDUCTION PATHWAYS M. Woan, G.Z. Yao, R. Venkataramanan, A. Thomson, S. Todo, T.E. Starzl, and R.J. Duquesnoy Divisions of Transplant Pathology, Pharn'~cy and Surgery University of Pittsburgh, Pittsburgh PA 15213 USA T cells and other lymphoid cells can be activated via different signal transduction pathways, as exemplified by CD3 or alloantigen as opposed to cytekine or phorbol ester-induced stimulation. Experimental immunosuppressive drugs which inhibit T cell proliferation may interfere with either of those pathways or with DNA replication. The purpose of this study was to assess the mode of action and the efficacy of various immunosuppressive drugs alone or in combination using in vitro culture systems. Drug ¢oncenirations ranged from 10-2 - 10 4 ng/ml. As p~vlously showa, cyclosporine A (102 ng/nd) and H¢,.506 (1 ng/ml) profoundly suppressed peripheral blood T cell responses to OKT3 and alloantigeas, but had no effect of cytokine (IL-2) or PMA-induo2d proliferation or growth of non-T col lines. MPA (102 ng/ml) and Bredinin (BR) (103 ng/ml), which beth inhibit guanine lmcleotide synthe~se, abrogated with equal efficacy lhe proliferalion of T and non-T ce~ls. Combination of low doses of FKS06 (10-2 ng/ml) and MPA 02-25 ng/ml) or BR (1200-2500 ng/ml) were mesfly additive, whereas at higher doses of either drug, the additive effect was lost. The broad spectrum of inhibitory effects seen with MPA and BR is due to inhibition of DNA synthesis through selective depletion of intracellular guanine nucleotide pools. Lymphoid cell populations which depend on de novo purine synthesis are mostly effecied by the~e drugs.
II1
#328 8.4
ANTIBODIES ELUTION STUDY FROM FAILED LIVER ALLOGRAFTS A Yagihashi, K Tanaka, K Noguchi, M Kobayashi, M Vanek, A Konno, T Takenaka, Y ¥oshida, TE Starzl and ¥ lwaki. University of Pittsburgh Tissue Typing I~beratory, Pittsburgh, PA. The deleterious effect of a positive T lymphocyte crossmatch in liver transplantation has b e e n demonstrated. In order to characterize the antibody deposited t o t he failed grafts, we further analized the acid eluates from the 30 failed liver a11ografts (20 patients with primary liver allograft and I0 with 2nd or more). There were 8 recipients transplanted across positive T cell orossmatches (5 in primary and 3 in regrafts) using DTT treated sera. T lymphocytotoxic reactivities w e r e demonstrated in 9 eluates from the p r i m a r y a l l o g r a f t s and in 3 from the regrafts, which was not influenced by the presence of preformed antibodies. Although only one eluate showed the specificity against the missmatched HI& antigens, the HLA specificities were n o t assigned in the remaining eluates. ~n addition, 3 eluates revealed platelet specific reaotivities. In conclusion, some other transplantation antigens besides H L A m i g h t be involved in liver allograft failure.
#329 8.7
EFFECTS OF IMMUNOSUPPRESSIVE MACROLIDES AND NUCLEOT1DE SYNTHETASE INHIBITORS ON PROLIFERATION OF LYMPHOID CELLS INDUCED VIA DISTINCT SIGNAL TRANSDUCTION PATHWAYS M. Woan, G.Z. Yao, R. Venkataramanan, A. Thomson, S. Todo, T.E. Starzl, and R.J. Duquesnoy Divisions of Transplant Pathology, Pharn'~cy and Surgery University of Pittsburgh, Pittsburgh PA 15213 USA T cells and other lymphoid cells can be activated via different signal transduction pathways, as exemplified by CD3 or alloantigen as opposed to cytekine or phorbol ester-induced stimulation. Experimental immunosuppressive drugs which inhibit T cell proliferation may interfere with either of those pathways or with DNA replication. The purpose of this study was to assess the mode of action and the efficacy of various immunosuppressive drugs alone or in combination using in vitro culture systems. Drug ¢oncenirations ranged from 10-2 - 10 4 ng/ml. As p~vlously showa, cyclosporine A (102 ng/nd) and H¢,.506 (1 ng/ml) profoundly suppressed peripheral blood T cell responses to OKT3 and alloantigeas, but had no effect of cytokine (IL-2) or PMA-induo2d proliferation or growth of non-T col lines. MPA (102 ng/ml) and Bredinin (BR) (103 ng/ml), which beth inhibit guanine lmcleotide synthe~se, abrogated with equal efficacy lhe proliferalion of T and non-T ce~ls. Combination of low doses of FKS06 (10-2 ng/ml) and MPA 02-25 ng/ml) or BR (1200-2500 ng/ml) were mesfly additive, whereas at higher doses of either drug, the additive effect was lost. The broad spectrum of inhibitory effects seen with MPA and BR is due to inhibition of DNA synthesis through selective depletion of intracellular guanine nucleotide pools. Lymphoid cell populations which depend on de novo purine synthesis are mostly effecied by the~e drugs.