Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions.
Chung, Y; Tanaka, S; Chu, F; Nurieva, RI; Martinez, GJ; Rawal, S; Wang, YH; Lim, H; Reynolds, JM; Zhou, XH; Fan, HM; Liu, ZM; Neelapu, SS; Dong, C
Nature medicine
17
983-8
2010
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Foxp3(+) regulatory T (T(reg)) cells suppress different types of immune responses to help maintain homeostasis in the body. How T(reg) cells regulate humoral immunity, including germinal center reactions, is unclear. Here we identify a subset of T(reg) cells expressing CXCR5 and Bcl-6 that localize to the germinal centers in mice and humans. The expression of CXCR5 on T(reg) cells depends on Bcl-6. These CXCR5(+)Bcl-6(+) T(reg) cells are absent in the thymus but can be generated de novo from CXCR5(-)Foxp3(+) natural T(reg) precursors. A lack of CXCR5(+) T(reg) cells leads to greater germinal center reactions including germinal center B cells, affinity maturation of antibodies and the differentiation of plasma cells. These results unveil a Bcl-6-CXCR5 axis in T(reg) cells that drives the development of follicular regulatory T (T(FR)) cells that function to inhibit the germinal center reactions. | 21785430
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Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells.
Thornton, AM; Korty, PE; Tran, DQ; Wohlfert, EA; Murray, PE; Belkaid, Y; Shevach, EM
Journal of immunology (Baltimore, Md. : 1950)
184
3433-41
2009
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Helios, a member of the Ikaros transcription factor family, is preferentially expressed at the mRNA level by regulatory T cells (Treg cells). We evaluated Helios protein expression using a newly generated mAb and demonstrated that it is expressed in all thymocytes at the double negative 2 stage of thymic development. Although Helios was expressed by 100% of CD4(+)CD8(-)Foxp3(+) thymocytes, its expression in peripheral lymphoid tissues was restricted to a subpopulation ( approximately 70%) of Foxp3(+) T cells in mice and humans. Neither mouse nor human naive T cells induced to express Foxp3 in vitro by TCR stimulation in the presence of TGF-beta expressed Helios. Ag-specific Foxp3(+) T cells induced in vivo by Ag feeding also failed to express Helios. Collectively, these results demonstrate that Helios is potentially a specific marker of thymic-derived Treg cells and raises the possibility that a significant percentage of Foxp3(+) Treg cells are generated extrathymically. | 20181882
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