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Mycobacteria‐induced Gr‐1 + subsets from distinct myeloid lineages have opposite effects on T cell expansion
Author(s) -
Dietlin Therese A.,
Hofman Florence M.,
Lund Brett T.,
Gilmore Wendy,
Stohlman Stephen A.,
Van der Veen Roel C.
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1006640
Subject(s) - biology , microbiology and biotechnology , t cell , intracellular , myeloid , population , splenocyte , immunology , immune system , demography , sociology
Similar to the regulation of vasodilation, the balance between NO and superoxide (O 2 – ) regulates expansion of activated T cells in mice. Reduction of suppressive NO levels by O 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 + 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 O 2 – . However, mostly granulocytic Ly‐6G + cells produced O 2 – 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 O 2 – interaction. Coculture of p47 phox −/− 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.