Mycobacteria-induced Gr-1+ subsets from distinct myeloid lineages have opposite effects on T cell expansion

Abstract

Abstract Similar to the regulation of vasodilation, the balance between NO and superoxide (O2–) regulates expansion of activated T cells in mice. Reduction of suppressive NO levels by O2– is essential for T cell expansion and development of autoimmunity. In mice primed with heat-killed Mycobacterium, a splenocyte population positive for Gr-1 (Ly-6G/C) is the exclusive source of both immunoregulatory free radicals. Distinct Gr-1+ cell subpopulations were separated according to Ly-6G expression. In culture with activated T cells, predominantly monocytic Ly-6G− Gr-1+ cells produced T cell-inhibitory NO but no O2–. However, mostly granulocytic Ly-6G+ cells produced O2– simultaneously but had no measurable effect on proliferation. Recombination of the two purified Gr-1+ subpopulations restored controlled regulation of T cell proliferation through NO and O2– interaction. Coculture of p47phox−/− and inducible NO synthase−/− Gr-1+ cells confirmed this intercellular interaction. These data suggest that bacterial products induce development of distinct Gr-1+ myeloid lineages, which upon stimulation by activated T cells, interact via their respective free radical products to modulate T cell expansion.

Keywords

Affiliated Institutions

• Cleveland Clinic US
• University of Southern California US

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