Regulation of the Germinal Center Reaction by Foxp3+ Follicular Regulatory T Cells
Regulation of the Germinal Center Reaction by Foxp3+ Follicular Regulatory T Cells
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DOI：
10.4049/jimmunol.1101328
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发表时间：
2011-11-01
影响因子：
4.4
通讯作者：
Graca, Luis
中科院分区：
文献类型：
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作者：
Wollenberg, Ivonne;Agua-Doce, Ana;Graca, Luis
滤泡辅助性T（T-FH）细胞参与体液应答，向生殖中心B细胞提供选择信号。最近，CXCR 5、PD-1和转录因子Bcl-6的表达允许鉴定TFH细胞。我们发现，一部分滤泡T细胞，具有T-FH细胞的表型特征并表达Foxp 3，在生发中心（GC）反应过程中被招募。这些Foxp 3（+）细胞来源于天然调节性T细胞。为了确定Foxp 3（+）滤泡T细胞的体内生理重要性，我们使用了CXCR 5缺陷型Foxp 3（+）细胞，其不能进入滤泡区域。CXCR 5缺陷型Foxp 3（+）细胞的连续细胞转移表明，Foxp 3（+）滤泡T细胞是用胸腺依赖性Ag免疫后GC反应的重要调节剂。我们的体内数据显示Foxp 3（+）滤泡T细胞可以限制GC反应的幅度以及分泌的Ag特异性IgM、IgG 1、IgG 2b和伊加的量。因此，Foxp 3（+）滤泡调节性T细胞似乎结合了T-FH和调节性T细胞的联合收割机特征，用于控制体液免疫应答。免疫学杂志，2011，187：4553-4560。
Follicular helper T (T-FH) cells participate in humoral responses providing selection signals to germinal center B cells. Recently, expression of CXCR5, PD-1, and the transcription factor Bcl-6 has allowed the identification of TFH cells. We found that a proportion of follicular T cells, with phenotypic characteristics of T-FH cells and expressing Foxp3, are recruited during the course of a germinal center (GC) reaction. These Foxp3(+) cells derive from natural regulatory T cells. To establish the in vivo physiologic importance of Foxp3(+) follicular T cells, we used CXCR5-deficient Foxp3(+) cells, which do not have access to the follicular region. Adoptive cell transfers of CXCR5-deficient Foxp3(+) cells have shown that Foxp3(+) follicular T cells are important regulators of the GC reaction following immunization with a thymus-dependent Ag. Our in vivo data show that Foxp3(+) follicular T cells can limit the magnitude of the GC reaction and also the amount of secreted Ag-specific IgM, IgG1, IgG2b, and IgA. Therefore, Foxp3(+) follicular regulatory T cells appear to combine characteristics of T-FH and regulatory T cells for the control of humoral immune responses. The Journal of Immunology, 2011, 187: 4553-4560.