A purified protein from Salmonella typhimurium inhibits proliferation of murine splenic anti-CD3 antibody-activated T-lymphocytes.
In previous study, we observed that the purified substance Salmonella typhimurium-derived inhibitor of T-cell proliferation (STI) had an immunosuppressive effect, demonstrated as the suppression of mitogenic lectin-induced proliferation of murine spleen cells. In the present study, we confirmed the immunosuppressive effect of STI, which suppressed 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 (IFN-gamma) secretion and inhibition of interleukin-2 (IL-2) secretion. Furthermore, the augmentation of IFN-gamma secretion caused IL-2 receptor 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. Furthermore, Western blotting using an anti-phosphotyrosine Ab showed that IL-2R-mediated tyrosine phosphorylation of protein substrates in T-cells was inhibited by incubation with STI for 48 h and this inhibition was not reversed by adding the anti-IFN-gamma Ab and rIL-2. These results suggest that STI-induced suppression of T-cell proliferation involves a defect in IL-2R function and/or IL-2 signaling pathway in T-cells.
Matsui
K
K
Department of Microbiology, Meiji College of Pharmacy, Tokyo, Japan.
D000818:Animals; D001426:Bacterial Proteins; D017252:CD3 Complex / Q000378:metabolism*; D002478:Cells, Cultured; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D012486:Salmonella typhimurium / Q000737:chemistry* / Q000472:pathogenicity; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism
D001426:Bacterial Proteins; D017252:CD3 Complex; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D014443:Tyrosine; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate