Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host.
The accumulation of myeloid suppressor cells (MSCs) is associated with immune suppression in tumor-bearing mice and in cancer patients. The suppressive activity of MSC correlates with the expression of the myeloid markers Gr-1, CD115 (macrophage colony-stimulating factor receptor), and F4/80. Gr-1(+)CD115(+) MSCs, in addition to being able to suppress T-cell proliferation in vitro, can induce the development of Foxp3(+) T regulatory cells (Treg) in vivo, which are anergic and suppressive. Furthermore, the secretion of interleukin (IL)-10 and transforming growth factor-beta by Gr-1(+)CD115(+) MSCs was induced and enhanced, respectively, on IFN-gamma stimulation. The development of Treg requires antigen-associated activation of tumor-specific T cells, depends on the presence of IFN-gamma and IL-10, and is independent of the nitric oxide-mediated suppressive mechanism by MSC. Our data provide evidence that Gr-1(+)CD115(+) MSC can mediate the development of Treg in tumor-bearing mice and show a novel immune suppressive mechanism by which MSCs can suppress antitumor responses.
Huang
Bo
B
Departments of Gene and Cell Medicine and General Surgery, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
Pan
Ping-Ying
PY
Li
Qingsheng
Q
Sato
Alice I
AI
Levy
David E
DE
Bromberg
Jonathan
J
Divino
Celia M
CM
Chen
Shu-Hsia
SH
D000818:Animals; D049109:Cell Proliferation; D017635:Clonal Anergy / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D007165:Immunosuppression Therapy; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016186:Receptor, Macrophage Colony-Stimulating Factor; D019707:Receptors, Chemokine; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory; D014162:Transfection; D014407:Tumor Cells, Cultured
D016207:Cytokines; D019707:Receptors, Chemokine; D016186:Receptor, Macrophage Colony-Stimulating Factor