eISSN 2329-0358


Get your full text copy in PDF

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

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.

This paper has been published under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially.
I agree