CD25− T Cells Generate CD25+Foxp3+ Regulatory T Cells by Peripheral Expansion

Abstract

Naturally occurring CD4+ regulatory T cells are generally identified through their expression of CD25. However, in several experimental systems considerable Treg activity has been observed in the CD4+CD25− fraction. Upon adoptive transfer, the expression of CD25 in donor-derived cells is not stable, with CD4+CD25+ cells appearing in CD4+CD25− T cell-injected animals and vice versa. We show in this study that CD25+ cells arising from donor CD25− cells upon homeostatic proliferation in recipient mice express markers of freshly isolated Treg cells, display an anergic state, and suppress the proliferation of other cells in vitro. The maintenance of CD25 expression by CD4+CD25+ cells depends on IL-2 secreted by cotransferred CD4+CD25− or by Ag-stimulated T cells in peripheral lymphoid organs.

CD4+CD25+ Treg induction by an HSP60‐derived peptide SJMHE1 from Schistosoma japonicum is TLR2 dependent

“…Recent studies have shown that CD4 1 CD25 1 T cells can be expanded in vivo and in vitro upon antigen stimulation [37,38]. Moreover, CD4 1 CD25 1 Treg can be induced from CD4 1 CD25 -T cells [26,27]. To further test whether CD4 1 CD25 -T cells can be differentiated into CD4 1 CD25 1 Foxp3 1 Treg by this peptide, we purified CD4 1 CD25 -T cells from mice and treated with SJMHE1 or OVA 323-339 in vitro.…”

“…No significant increases in CD4 1 CD25 1 Foxp3 1 T cells were observed in OVA 323-339 stimulated cells. Studies have shown that CD4 1 CD25 1 Treg cells can be induced from CD4 1 CD25 -T cells [26,27]. To further test whether CD4 1 CD25 -T cells can be differentiated into CD25 1 /Foxp3 1 Treg by SJMHE1, CD4 1 CD25 -T cells were purified and stimulated in vitro with SJMHE1.…”

Immunological mechanisms and clinical implications of regulatory T cell deficiency in a systemic autoimmune disorder: Roles of IL‐2 versus IL‐15

“…Foxp3 transduction may convert naive CD4 + CD25 -T cells into CD25 + regulatory cells with suppressive activity. Expression of Foxp3 can also be induced in CD4 + CD25 -T cells upon activation [29] or in the presence of TGF-b [30,31]. These findings suggest that the microenvironment could influence the expression of Foxp3 during an immune response, inducing and promoting the expansion of peripheral Treg, also known as the adaptive Treg [29].…”

Regulatory T Cell Deficiency in Systemic Autoimmune Disorders – Causal Relationship and Underlying Immunological Mechanisms

“…Foxp3 transduction has been shown to convert naive CD4 + CD25 -T cells into CD25 + regulatory cells with suppressive activity [22]. Expression of Foxp3 can also be induced in CD4 + CD25 -T cells upon activation [27] or in the presence of TGF-ß [28,29]. These findings suggest that the microenvironment could influence the expression of Foxp3 during an immune response, inducing and promoting the expansion of peripheral Treg, also known as the inducible or adaptive Treg cells [27].…”

“…Expression of Foxp3 can also be induced in CD4 + CD25 -T cells upon activation [27] or in the presence of TGF-ß [28,29]. These findings suggest that the microenvironment could influence the expression of Foxp3 during an immune response, inducing and promoting the expansion of peripheral Treg, also known as the inducible or adaptive Treg cells [27]. Treg may exert their immunosuppressive effects through cell-cell contacts and by the release of immunosuppressive cytokines such as IL-10 and TGF- [30].…”