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

被引：632

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

来源：

IMMUNITY | 2013年 / 39卷 / 04期

基金：

澳大利亚国家健康与医学研究理事会; 中国国家自然科学基金; 澳大利亚研究理事会; 北京市自然科学基金; 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：

071005 [微生物学]; 100108 [医学免疫学];

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

页码：770 / 781

页数：12

共 49 条

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