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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-? 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-? 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.

SUBMITTER: Zhang X

PROVIDER: S-EPMC3796486 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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CD4(+)CD62L(+) central memory T cells can be converted to Foxp3(+) T cells.

Zhang Xiaolong X Chang Li Xian X Xiao Xiang X Sun Rui R Tian Zhigang Z Wei Haiming H

PloS one 20131014 10

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, s ...[more]

PMID: 24155942

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Project description:UnlabelledInterleukin 2 (IL-2) signaling through the IL-2 receptor alpha chain (CD25) facilitates HIV replication in vitro and facilitates homeostatic proliferation of CD25(+) FoxP3(+) CD4(+) T cells. CD25(+) FoxP3(+) CD4(+) T cells may therefore constitute a suitable subset for HIV infection and plasma virion production. CD25(+) FoxP3(+) CD4(+) T cell frequencies, absolute numbers, and the expression of CCR5 and cell cycle marker Ki67 were studied in peripheral blood from HIV(+) and HIV(-) study volunteers. Different memory CD4(+) T cell subsets were then sorted for quantification of cell-associated HIV DNA and phylogenetic analyses of the highly variable EnvV1V3 region in comparison to plasma-derived virus sequences. In HIV(+) subjects, 51% (median) of CD25(+) FoxP3(+) CD4(+) T cells expressed the HIV coreceptor CCR5. Very high frequencies of Ki67(+) cells were detected in CD25(+) FoxP3(+) memory CD4(+) T cells (median, 27.6%) in comparison to CD25(-) FoxP3(-) memory CD4(+) T cells (median, 4.1%; P < 0.0001). HIV DNA content was 15-fold higher in CD25(+) FoxP3(+) memory CD4(+) T cells than in CD25(-) FoxP3(-) T cells (P = 0.003). EnvV1V3 sequences derived from CD25(+) FoxP3(+) memory CD4(+) T cells did not preferentially cluster with plasma-derived sequences. Quasi-identical cell-plasma sequence pairs were rare, and their proportion decreased with the estimated HIV infection duration. These data suggest that specific cellular characteristics of CD25(+) FoxP3(+) memory CD4(+) T cells might facilitate efficient HIV infection in vivo and passage of HIV DNA to cell progeny in the absence of active viral replication. The contribution of this cell population to plasma virion production remains unclear.ImportanceDespite recent advances in the understanding of AIDS virus pathogenesis, which cell subsets support HIV infection and replication in vivo is incompletely understood. In vitro, the IL-2 signaling pathway and IL-2-dependent cell cycle induction are essential for HIV infection of stimulated T cells. CD25(+) FoxP3(+) memory CD4 T cells, often referred to as regulatory CD4 T cells, depend on IL-2 signaling for homeostatic proliferation in vivo Our results show that CD25(+) FoxP3(+) memory CD4(+) T cells often express the HIV coreceptor CCR5, are significantly more proliferative, and contain more HIV DNA than CD25(-) FoxP3(-) memory CD4 T cell subsets. The specific cellular characteristics of CD25(+) FoxP3(+) memory CD4(+) T cells probably facilitate efficient HIV infection in vivo and passage of HIV DNA to cell progeny in the absence of active viral replication. However, the contribution of this cell subset to plasma viremia remains unclear.

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CD4(+)CD62L(+) central memory T cells can be converted to Foxp3(+) T cells.

Publications

CD4(+)CD62L(+) central memory T cells can be converted to Foxp3(+) T cells.

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