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.
Isakov
N
N
Department of Microbiology and Immunology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Tamir
A
A
el-On
J
J
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D001685:Biological Factors / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured / Q000276:immunology / Q000378:metabolism; D003208:Concanavalin A / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D018320:Leishmania major / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000187:drug effects* / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013491:Suppressor Factors, Immunologic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology*
D000953:Antigens, Protozoan; D001685:Biological Factors; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D013491:Suppressor Factors, Immunologic; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D003208:Concanavalin A