Mycobacteria-induced Gr-1+ subsets from distinct myeloid lineages have opposite effects on T cell expansion.
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.
Dietlin
Therese A
TA
Department of Neurology, University of Southern California Keck School of Medicine, MCA 245, 1333 San Pablo Street, Los Angeles, CA 90033, USA.
Hofman
Florence M
FM
Lund
Brett T
BT
Gilmore
Wendy
W
Stohlman
Stephen A
SA
van der Veen
Roel C
RC
D000818:Animals; D019070:Cell Lineage / Q000276:immunology*; D049109:Cell Proliferation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D022423:Myeloid Cells / Q000145:classification / Q000276:immunology*; D009569:Nitric Oxide / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000172:deficiency; D019707:Receptors, Chemokine / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D013481:Superoxides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
C503133:Gr-1 protein, mouse; D019707:Receptors, Chemokine; D013481:Superoxides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II