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

Similar to the regulation of vasodilation, the balance between NO and superoxide (O super(-) sub(2)) regulates expansion of activated T cells in mice. Reduction of suppressive NO levels by O super(-) sub(2) 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 super(+) cell subpopulations were separated according to Ly-6G expression. In culture with activated T cells, predominantly monocytic Ly-6G super(-) Gr-1 super(+) cells produced T cell-inhibitory NO but no O super(-) sub(2). However, mostly granulocytic Ly-6G super(+) cells produced O super(-) sub(2) simultaneously but had no measurable effect on proliferation. Recombination of the two purified Gr-1 super(+) subpopulations restored controlled regulation of T cell proliferation through NO and O super(-) sub(2) interaction. Coculture of p47 super(phox-/-) and inducible NO synthase super(-/-)Gr-1 super(+) cells confirmed this intercellular interaction. These data suggest that bacterial products induce development of distinct Gr-1 super(+) myeloid lineages, which upon stimulation by activated T cells, interact via their respective free radical products to modulate T cell expansion.