A CELL-FREE-EXTRACT OF SALMONELLA-TYPHIMURIUM INHIBITS MITOGEN-INDUCED PROLIFERATION OF MURINE SPLENIC T-LYMPHOCYTES

In this study, a cell-free extract of Salmonella inhibited T cell mito gen-induced proliferation of spleen cells from non-immunized mice. The proliferation of murine spleen cells stimulated with a T cell mitogen , such as phytohaemagglutinin (PHA) or concanavalin A (ConA) was suppr essed significantly when the cells were treated with a sonicate of S. typhimurium, but not of E. coli. The agent(s) responsible for the supp ressive effect existed mainly in the soluble fraction of S. typhimuriu m, whereas the membrane fraction possessed minimal activity. The T cel l proliferation suppression paralleled the level of interleukin-2 (IL- 2) secretion. Addition of phorbol 12-myristate-13 acetate (PMA) to the cultures restored IL-2 secretion to normal levels, although prolifera tion remained suppressed and was not reversed by treatment with recomb inant IL-2. These results suggest that the suppression of T cell proli feration induced by a soluble Salmonella fraction is associated with i nhibition of IL-2 secretion and the response of T cells to IL-2 and th e former effect is dependent upon the inhibition of the stimulatory ac tivity of protein kinase C on IL-2 secretion. This type of suppression may explain a mechanism of immunosuppression induced by murine typhoi d fever.