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Kinetics of in vitro immuneresponses of , and B cells during tolerance induction by sirolimus

R Ghobrial, M Karczewski, M Ferraresso, L Tian, S M Stepkowski, B D Kahan

Ann Transplant 1996; 1(4): 22-29

ID: 496681

Published: 1996-12-13


Objectives: The purpose of the study presented herein was to examine immune performances of rat heart allograft recipients immunosuppressed with sirolimus (SRL.rapamycin;Rapamune.Wyeth-Ayerst. Princeton, NJ). Methods: The immune performances of lymphocytes harvested from SRL-treated Wistar Furth (WF; RT I") recipients of Buffalo (BUF; RT Ib) heart allografts were examined on days 7. 14. and 90 postgrafting. Results: Whether derived from normal WF rats, SRL-treated WF heart recipients. or SRL-untreated WF heart recipients. pan- T cell populations purified from the lymph nodes or spleens on day 7 or 14 displayed similar responses to phytohemaglutinin. anti- T cell receptor R73 monoclonal antibody, donor-type BUF. or third-party Brown Norway alloantigenic stimulators. There was no in vitro evidence of suppressor T cells in SRL-treated recipients. The frequencies of anti-BUF-specific cytotoxic T cells. as shown by limiting dilution analysis, were similar in the short- (days 7 or 14) and in the long- (day 90) term surviving recipients. SRL treatment did not affect the expression of interleukin-2 (IL-2) messenger RNA (mRNA) by T helper I (Thl) or of IL-4 and IL-IO mRNA by Th2 cells on days 7 and 14 postgrafting, but did induce selective activation of Th2 cells on day 60 postgrafting. Administration of SRL induced the production of non-complement (C)-fixing IgG2c BUF-specific alloantibodies that appeared in the sera of unresponsive recipients on day 14 postgrafting and reached a peak concentration on day 120 postgrafting. In contrast to untreated recipients that rejected BUF heart allografts, all SRL-treated WF recipients failed to produce C-fixing BUF-specific alloantibodies. Conclusions: SRL promotes long-term selective activation of Th2 cells and the production of non-C -fixing IgG2c blocking antibodies.

Keywords: Sirolimus, immunosuppresion, Heart Transplantation, in vitro performances



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