title: CD4(+)CD62L(+) central memory T cells can be converted to Foxp3(+) T cells.
abstract: The peripheral Foxp3(+) Treg pool consists of naturally arising Treg (nTreg) and adaptive Treg cells (iTreg). It is well known that naive CD4(+) T cells can be readily converted to Foxp3(+) iTreg in vitro, and memory CD4(+) T cells are resistant to conversion. In this study, we investigated the induction of Foxp3(+) T cells from various CD4(+) T-cell subsets in human peripheral blood. Though naive CD4(+) T cells were readily converted to Foxp3(+) T cells with TGF-β and IL-2 treatment in vitro, such Foxp3(+) T cells did not express the memory marker CD45RO as do Foxp3(+) T cells induced in the peripheral blood of Hepatitis B Virus (HBV) patients. Interestingly, a subset of human memory CD4(+) T cells, defined as CD62L(+) central memory T cells, could be induced by TGF-β to differentiate into Foxp3(+) T cells. It is well known that Foxp3(+) T cells derived from human CD4(+)CD25(-) T cells in vitro are lack suppressive functions. Our data about the suppressive functions of CD4(+)CD62L(+) central memory T cell-derived Foxp3(+) T cells support this conception, and an epigenetic analysis of these cells showed a similar methylation pattern in the FOXP3 Treg-specific demethylated region as the naive CD4(+) T cell-derived Foxp3(+) T cells. But further research showed that mouse CD4(+) central memory T cells also could be induced to differentiate into Foxp3(+) T cells, such Foxp3(+) T cells could suppress the proliferation of effector T cells. Thus, our study identified CD4(+)CD62L(+) central memory T cells as a novel potential source of iTreg.
authors.affiliation: Institute of Immunology, School of Life Sciences, University of Science & Technology of China, Hefei, Anhui, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Zhang
authors.forename: Xian
authors.initials: X
authors.lastname: Chang Li
authors.forename: Xiang
authors.initials: X
authors.lastname: Xiao
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
authors.forename: Haiming
authors.initials: H
authors.lastname: Wei
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D019041:L-Selectin / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; D011948:Receptors, Antigen, T-Cell; D016212:Transforming Growth Factor beta; D019041:L-Selectin; D017493:Leukocyte Common Antigens