Immunity
Volume 34, Issue 1, 28 January 2011, Pages 108-121
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Article
Human Blood CXCR5+CD4+ T Cells Are Counterparts of T Follicular Cells and Contain Specific Subsets that Differentially Support Antibody Secretion

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Summary

Although a fraction of human blood memory CD4+ T cells expresses chemokine (C-X-C motif) receptor 5 (CXCR5), their relationship to T follicular helper (Tfh) cells is not well established. Here we show that human blood CXCR5+CD4+ T cells share functional properties with Tfh cells and appear to represent their circulating memory compartment. Blood CXCR5+CD4+ T cells comprised three subsets: T helper 1 (Th1), Th2, and Th17 cells. Th2 and Th17 cells within CXCR5+, but not within CXCR5, compartment efficiently induced naive B cells to produce immunoglobulins via interleukin-21 (IL-21). In contrast, Th1 cells from both CXCR5+ and CXCR5 compartments lacked the capacity to help B cells. Patients with juvenile dermatomyositis, a systemic autoimmune disease, displayed a profound skewing of blood CXCR5+ Th cell subsets toward Th2 and Th17 cells. Importantly, the skewing of subsets correlated with disease activity and frequency of blood plasmablasts. Collectively, our study suggests that an altered balance of Tfh cell subsets contributes to human autoimmunity.

Highlights

► Human blood CXCR5+CD4+ T cells have characteristics of circulating memory Tfh cells ► Human blood CXCR5+CD4+ T cells comprise three subsets: Th1, Th2, and Th17 cells ► Unlike CXCR5+ Th2 and Th17 cells, CXCR5+ Th1 cells do not help B cells ► CXCR5+ Th cell subsets are skewed toward Th2 and Th17 cells in juvenile dermatomyositis

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