INHIBITION OF MURINE SPLENIC AND MUCOSAL LYMPHOCYTE FUNCTION BY ENTERIC BACTERIAL PRODUCTS

Previously we shelved that lysates of enteropathogenic Escherichia col i (EPEC) inhibit lymphokine production by mitogen-activated human peri pheral blood and lamina propria mononuclear cells. The aims of the pre sent study were to determine whether EPEC-inhibitory factors have simi lar effects on murine lymphoid populations in order to further delinea te the mechanisms of alteration of cytokine production. Preexposure to EPEC lysates inhibited mitogen-stimulated interleukin-2 (IL-2), IL-4, and gamma interferon (IFN-gamma) production by murine spleen cells, b ut IL-10 production was increased. The inhibition,vas not due to incre ased apoptosis and was not blocked by neutralizating antibodies agains t IL-10 or transforming growth factor beta (TGF-beta), EPEC lysates al so inhibited mitogen-stimulated IL-2 and IFN-gamma production by CD11b depleted spleen cells, IL-2 and IL-4 production by intraepithelial an d Peyer's patch lymphocytes, IL-2 production by the human T-cell line Jurkat, and antigen-stimulated IL-2 production by murine spleen cells. Lysates obtained from Shiga-like toxin-producing E, coli, E, coli RDE C-1, Citrobacter rodentium, and an EPEC espB insertion mutant all inhi bited IL-2 and IL-4 production by mitogen-stimulated lymphoid cells. I n conclusion, lysates of EPEC and related bacteria directly inhibit cy tokine production by lymphoid cells from multiple sites by a mechanism that does not increase apoptosis or result from secondary effects of IL-10 or TGF-beta.