Circulating Precursor CCR7loPD-1hi CXCR5+ CD4+ T Cells Indicate Tfh Cell Activity and Promote Antibody Responses upon Antigen Reexposure

被引:555
作者
He, Jing [1 ]
Tsai, Louis M. [2 ]
Leong, Yew Ann [2 ]
Hu, Xin [2 ,3 ]
Ma, Cindy S. [4 ,5 ]
Chevalier, Nina [4 ,5 ,6 ]
Sun, Xiaolin [1 ]
Vandenberg, Kirsten [7 ]
Rockman, Steve [7 ]
Ding, Yan [1 ]
Zhu, Lei [1 ]
Wei, Wei [8 ]
Wang, Changqi [9 ]
Karnowski, Alexander [10 ]
Belz, Gabrielle T. [10 ]
Ghali, Joanna R. [11 ]
Cook, Matthew C. [3 ,12 ]
Riminton, D. Sean [13 ]
Veillette, Andre [14 ]
Schwartzberg, Pamela L. [15 ]
Mackay, Fabienne [16 ]
Brink, Robert [4 ,5 ]
Tangye, Stuart G. [4 ,5 ]
Vinuesa, Carola G. [3 ]
Mackay, Charles R. [2 ]
Li, Zhanguo [1 ]
Yu, Di [2 ]
机构
[1] Peking Univ, Peoples Hosp, Dept Rheumatol & Immunol, Beijing 100044, Peoples R China
[2] Monash Univ, Sch Biomed Sci, Mol Immunomodulat Lab, Clayton, Vic 3800, Australia
[3] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia
[4] Garvan Inst Med Res, Program Immunol, Darlinghurst, NSW 2010, Australia
[5] Univ New S Wales, St Vincents Clin Sch, Darlinghurst, NSW 2010, Australia
[6] Univ Med Ctr Freiburg, Dept Rheumatol & Clin Immunol, D-79106 Freiburg, Germany
[7] BioCSL, Influenza Res & Dev, Parkville, Vic 3052, Australia
[8] Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100190, Peoples R China
[9] Shandong Acad Sci, Shandong Anal & Test Ctr, Lab Immunol Environm & Hlth, Jinan 250014, Shandong, Peoples R China
[10] Walter & Eliza Hall Inst Med Res, Div Mol Immunol, Parkville, Vic 3052, Australia
[11] Monash Univ, Ctr Inflammatory Dis, Clayton, Vic 3800, Australia
[12] Australian Natl Univ, Sch Med, Canberra, ACT 2601, Australia
[13] Concord Hosp, Dept Immunol, Concord, NSW 2139, Australia
[14] Clin Res Inst Montreal, Montreal, PQ H2W 1R7, Canada
[15] NHGRI, Bethesda, MD 20892 USA
[16] Monash Univ, Dept Immunol, Clayton, Vic 3800, Australia
基金
澳大利亚国家健康与医学研究理事会; 北京市自然科学基金; 澳大利亚研究理事会; 中国国家自然科学基金; 英国医学研究理事会;
关键词
FOLLICULAR HELPER-CELL; CENTER B-CELL; CXC CHEMOKINE RECEPTOR-5; BCL6; EXPRESSION; CENTRAL MEMORY; EFFECTOR; GENERATION; DIFFERENTIATION; INTERLEUKIN-21; EXPANSION;
D O I
10.1016/j.immuni.2013.09.007
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Follicular B helper T (Tfh) cells support high affinity and long-term antibody responses. Here we found that within circulating CXCR5(+) CD4(+) T cells in humans and mice, the CCR7(lo)PD-1(hi) subset has a partial Tfh effector phenotype, whereas CCR7(hi) PD-1(lo) cells have a resting phenotype. The circulating CCR7(lo)PD-1(hi) subset was indicative of active Tfh differentiation in lymphoid organs and correlated with clinical indices in autoimmune diseases. Thus the CCR7(lo)PD-1(hi) subset provides a biomarker to monitor protective antibody responses during infection or vaccination and pathogenic antibody responses in autoimmune diseases. Differentiation of both CCR7(hi)PD-1(lo) and CCR7(lo)PD-1(hi) subsets required ICOS and BCL6, but not SAP, suggesting that circulating CXCR5(+) helper T cells are primarily generated before germinal centers. Upon antigen reencounter, CCR7(lo)PD-1(hi) CXCR5(+) precursors rapidly differentiate into mature Tfh cells to promote anti-body responses. Therefore, circulating CCR7(lo)PD-1(hi) CXCR5(+) CD4(+) T cells are generated during active Tfh differentiation and represent a new mechanism of immunological early memory.
引用
收藏
页码:770 / 781
页数:12
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