SELECTIVE DOWN-REGULATION OF TH2 IMMUNE-RESPONSES FOLLOWING TREATMENTWITH ANTIGEN-COUPLED SPLENOCYTES

Intravenous injection of antigen-coupled splenocytes has been widely u sed to induce specific tolerance to a variety of antigens. In this stu dy, we investigated the effects of such a treatment on Th1 and Th2 ant igen-specific immune responses. Using both well-characterized model an tigens and crude homogenates from Leishmania major promastigotes, we f ound that intravenous injection of antigen-coupled splenocytes strongl y down-regulated antigen-specific Th2 responses but had no or only mod erate effects on Th1 responses. Because the susceptibility of inbred s trains of mice to murine leishmaniasis has been found to be correlated with a strong Th2 response against parasite antigens, we investigated whether administration of splenocytes chemically coupled to parasite antigens could protect susceptible mice from murine leishmaniasis. We found that this was indeed the case and further demonstrated that prot ection was associated with a strong decrease in the number of parasite -specific Th2-like cells. Because administration of antigen-coupled sp lenocytes is believed to induce ligation of the T cell receptor comple x without inducing a co-stimulatory signal, our results further sugges t that priming of Th1 cells is less dependent on co-stimulatory signal s than the priming of Th2 cells.