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 major was found to suppress ConA-induced polyclonal activation of mouse T cells. To further dissect the effect of EF on cell-mediated immune responses, we used in vivo primed antigen-specific murine lymph node cells. EF inhibited the proliferative response of keyhole limpet hemocyanin (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 cells 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 events in the activation process of T cells, we used IL2-R positive T cells 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-dependent manner. The data suggest, therefore, that the locus of inhibitory effect of EF is at both the early and late stages of T cell activation and apparently involves two different signal transduction pathway linked to the receptors for the antigen and IL2.