MECHANISMS OF HSP65 EXPRESSION INDUCED BY GAMMA-DELTA T-CELLS IN MURINE TOXOPLASMA-GONDII INFECTION

We have previously reported that the expression of an endogenous 65-kD heat shock protein (HSP65) in macrophages is closely correlated with the protection against infection by Toxoplasma gondii in mice, and gam ma delta T cells play a critical role in the expression of this protei n. In this study, we investigated how gamma delta T cells contribute t o the protection and HSP65 expression. After intraperitoneal infection with bradyzoites of the Beverley strain of T. gondii, mRNA encoding I FN-gamma and TNF-alpha was detected in the peritoneal gamma delta T ce lls by RT-PCR technique, and macrophages that produced nitric oxide (N O) and expressed HSP65 were also detected. Depletion of gamma delta T cells resulted in suppression of NO production by macrophages, and it also inhibited HSP65 expression. HSP65 expression, however, does not a ppear to be induced by stimulation with NO, since treatment with N-G-m onomethylarginine, an inhibitor of NO synthesis, did not attenuate the expression of HSP65. This expression was completely suppressed when m ice were simultaneously treated with anti-IFN-gamma and anti-TNF-alpha although either antibody alone was less effective. The synergistic ef fect of these cytokines was also demonstrated by an in vitro experimen t, in which peritoneal macrophages were cultured with recombinant IFN- gamma and TNF-alpha. These results indicate that gamma delta T cells, which protect against infection with T. gondii induce the expression o f HSP65 by secreting IFN-gamma and TNF-alpha and the production of NO, and that the expression of HSP65 is independent of inflammatory chemi cal compounds like NO and H2O2.