A PURIFIED PROTEIN FROM SALMONELLA-TYPHIMURIUM INHIBITS PROLIFERATIONOF MURINE SPLENIC ANTI-CD3 ANTIBODY-ACTIVATED T-LYMPHOCYTES

In a previous study, we observed that the purified substance Salmonell a typhimurium-derived inhibitor of T-cell proliferation (STI) had an i mmunosuppressive effect, demonstrated as the suppression of mitogenic lectin-induced proliferation of murine spleen cells. In the present st udy, we confirmed the immunosuppressive effect of STI; which suppresse d the proliferation of murine splenic T-lymphocytes activated with the anti-CD3 antibody (Ab) and phorbol 12-myristate-13 acetate (PMA) and this phenomenon was accompanied by augmentation of interferon-gamma (I FN-gamma) secretion and inhibition of interleukin-2 (IL-2) secretion. Furthermore, the augmentation of IFN-gamma secretion caused IL-2 recep tor alpha chain (IL-2R alpha) over expression on T-cells. However, the addition of an anti-IFN-gamma Ab and recombinant IL-2 (rIL-2) did not reverse the suppressed T-cell proliferation, although the level of IL -2R alpha expression on T-cells recovered to around normal. Furthermor e, Western blotting using an anti-phosphotyrosine Ab showed that IL-2R -mediated tyrosine phosphorylation of protein substrates in T-cells wa s inhibited by incubation with STI for 48 h and this inhibition was no t reversed by adding the anti-IFN-gamma Ab and rIL-2. These results su ggest that STI-induced suppression of T-cell proliferation involves a defect in IL-2R function and/or IL-2 signaling pathway in T-cells.