Priming by microbial antigens from the intestinal flora determines the ability of CD4(+) T cells to rapidly secrete IL-4 in BALB/c mice infected withLeishmania major

Infection of BALB/c mice with Leishmania major results in the rapid accumul ation of IL-4 transcripts within CD4(+) T cells that react to the parasite Leishmania homologue of mammalian RACK1 (LACK) Ag, Because memory/effector cells secrete IL-4 more rapidly than naive cells, we sought to analyze the phenotype of these lymphocytes before infection. Indeed, a fraction of LACK -specific CD4(+) T cells expressed a typical CD62 ligand(low)CD44(high)CD45 RB(low) phenotype in uninfected mice. LACK-specific T cells were primed in gut-associated lymphoid tissues by cross-reactive microbial Ags as demonstr ated by their reactivity with bacterial extracts and by the ability of APCs from the mesenteric LN of BALB/c mice to induce their proliferation. Also, mice in which the digestive tract has been decontaminated exhibited a redu ced proportion of LACK-specific T cells expressing a memory/effector phenot ype and did not exhibit the early accumulation of IL-4 transcripts induced by L. major. Thus, LACK-specific T cells represent a subset of CD4(+) T cel ls which have acquired the ability to rapidly secrete IL-4 as the result of their priming by cross-reactive microbial Ags, Tracking the fate of these cells may provide information about the regulation of cell-mediated immune responses to gut Ags in physiological and pathological situations.