Identification and characterization of Foxp3(+) gammadelta T cells in mouse and human.
Regulatory T cells (Tregs) expressing TCRalphabeta play a critical role in the maintenance of the immune system homeostasis. Tregs express the cell surface markers CD4 and CD25 as well as the transcription factor Foxp3. Foxp3(+)CD4(+)CD25(+)TCRalphabeta(+) Tregs can be generated from mouse and human CD4(+)CD25(-) T cells in vitro via TGF-beta induction. As growing evidences suggest that gammadelta T cells also have immunoregulatory function, we have attempted to identify and characterize Foxp3(+) cells in mouse and human gammadelta T cells. We found that freshly isolated mouse splenic gammadelta T cells did not express Foxp3. When mouse splenocytes were stimulated with anti-TCRgammadelta in the presence of TGF-beta, a population of Foxp3(+) gammadelta T cells appeared, in most of which expressed CD25 as well. Compared with CD25(-) gammadelta T cells, TGF-beta induced CD25(+) gammadelta T cells not only expressed Foxp3, but also had increased TGF-beta and GITR expression. Furthermore, the TGF-beta induced gammadelta T cells mediated a potent immunosuppressive effect on anti-CD3 stimulated T cell activation and proliferation. In contrast, although a small fraction of human peripheral blood and tumor infiltrating gammadelta T cells expressed Foxp3, similar culture condition with anti-TCRgammadelta plus TGF-beta failed to generate functional human Foxp3(+) gammadelta T cells. In conclusion, our results suggest that mouse splenic Foxp3(+) gammadelta T cells with suppressive function can be induced by TCR and TGF-beta costimulation, whereas functional human Foxp3(+) gammadelta T cells in peripheral blood could not be generated under the same condition.
Kang
Ning
N
Department of Immunology, School of Basic Medicine, Peking Union Medical College, and Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, 5 Dong Dan San Tiao, Beijing 100005, China.
Tang
Long
L
Li
Xiaoyan
X
Wu
Dan
D
Li
Wenjing
W
Chen
Xingming
X
Cui
Lianxian
L
Ba
Denian
D
He
Wei
W
D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000096:biosynthesis; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006801:Humans; D007108:Immune Tolerance; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D017252:CD3 Complex; D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053450:Glucocorticoid-Induced TNFR-Related Protein; D053645:Interleukin-2 Receptor alpha Subunit; D016692:Receptors, Antigen, T-Cell, gamma-delta; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C491405:TNFRSF18 protein, human; D016212:Transforming Growth Factor beta