TY - JOUR
T1 - Human Blood CXCR5+CD4+ T Cells Are Counterparts of T Follicular Cells and Contain Specific Subsets that Differentially Support Antibody Secretion
AU - Morita, Rimpei
AU - Schmitt, Nathalie
AU - Bentebibel, Salah Eddine
AU - Ranganathan, Rajaram
AU - Bourdery, Laure
AU - Zurawski, Gerard
AU - Foucat, Emile
AU - Dullaers, Melissa
AU - Oh, SangKon
AU - Sabzghabaei, Natalie
AU - Lavecchio, Elizabeth M.
AU - Punaro, Marilynn
AU - Pascual, Virginia
AU - Banchereau, Jacques
AU - Ueno, Hideki
N1 - Funding Information:
We thank E. Kowalski and S. Coquery for cell sorting; L. Walters for cell processing from apheresis blood; S. Zurawski for IL-21 Luminex analysis; and I. Munagala for real-time RT-PCR. We thank A. Karolina Palucka for critical reading and discussions. This study was supported by U19-AI057234, R01-CA84512, R01-CA078846, AR054083-01 (J.B.), U19-AI082715-01 (H.U., Program PI: V.P.), and Baylor Health Care System (H.U. and J.B.). J.B. holds the W.W. Caruth, Jr., Chair for Transplantation Immunology Research.
PY - 2011/1/28
Y1 - 2011/1/28
N2 - 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.
AB - 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.
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U2 - 10.1016/j.immuni.2010.12.012
DO - 10.1016/j.immuni.2010.12.012
M3 - Article
C2 - 21215658
AN - SCOPUS:78751690647
SN - 1074-7613
VL - 34
SP - 108
EP - 121
JO - Immunity
JF - Immunity
IS - 1
ER -