Cutting edge: human latency-associated peptide+ T cells: a novel regulatory T cell subset.
Regulatory T cells (Tregs) play an important role in the maintenance of peripheral tolerance. Several molecules including TGF-beta have been linked to the function and differentiation of Tregs. In this study, we describe a unique population of T cells expressing a membrane bound form of TGF-beta, the latency-associated peptide (LAP), and having regulatory properties in human peripheral blood. These CD4(+)LAP(+) T cells lack Foxp3 but express TGF-betaR type II and the activation marker CD69. CD4(+)LAP(+) T cells are hypoproliferative compared with CD4(+)LAP(-) T cells, secrete IL-8, IL-9, IL-10, IFN-gamma, and TGF-beta upon activation, and exhibit TGF-beta- and IL-10-dependent suppressive activity in vitro. The in vitro activation of CD4(+)LAP(-) T cells results in the generation of LAP(+) Tregs, which is further amplified by IL-8. In conclusion, we have characterized a novel population of human LAP(+) Tregs that is different from classic CD4(+)Foxp3(+)CD25(high) natural Tregs.
Gandhi
Roopali
R
Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.
Farez
Mauricio F
MF
Wang
Yue
Y
Kozoriz
Deneen
D
Quintana
Francisco J
FJ
Weiner
Howard L
HL
D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D015415:Biomarkers / Q000097:blood; D015704:CD4 Antigens / Q000096:biosynthesis / Q000097:blood; D002478:Cells, Cultured; D018920:Coculture Techniques; D051858:Forkhead Transcription Factors / Q000097:blood / Q000172:deficiency; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology; D037181:Lectins, C-Type / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D048008:TNF Receptor-Associated Factor 3; D053781:Transforming Growth Factor beta2 / Q000096:biosynthesis* / Q000097:blood; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015415:Biomarkers; D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; D016753:Interleukin-10; D037181:Lectins, C-Type; D048008:TNF Receptor-Associated Factor 3; D053781:Transforming Growth Factor beta2; D000099192:CD69 Antigens; C418974:FOXP3 protein, human; C508609:IL10 protein, human