SUPPRESSION OF ANTIGEN-SPECIFIC T-CELL RESPONSES BY LEISHMANIA-MAJOR EXCRETED FACTOR - INHIBITION OF ACTIVATION SIGNALS LINKED TO THE T-CELL ANTIGEN RECEPTOR AND INTERLEUKIN-2 RECEPTOR

An excreted factor (EF) derived from culture medium of Leishmania majo r was found to suppress ConA-induced polyclonal activation of mouse T cells. To further dissect the effect of EF on cell-mediated immune res ponses, we used in vivo primed antigen-specific murine lymph node cell s. EF inhibited the proliferative response of keyhole limpet hemocyani n (KLH) or ovalbumin (OA)-primed T cells upon in vitro challenge with the antigen. In addition, it suppressed the induction of interleukin 2 receptor (IL2-R) alpha following mitogen stimulation of unprimed T ce lls or antigen challenge of KLH-primed T cells. Thus, EF affects early events in signal transduction that follow the T cell antigen receptor (TCR) Triggering. To test whether EF may interfere with more remote e vents in the activation process of T cells, we used IL2-R positive T c ells and tested their response to IL2 in the presence of EF. We found that EF inhibited also IL2-dependent T cell proliferation in a dose-de pendent manner. The data suggest, therefore, that the locus of inhibit ory effect of EF is at both the early and late stages of T cell activa tion and apparently involves two different signal transduction pathway linked to the receptors for the antigen and IL2.