Circulating precursor CCR7(lo)PD-1(hi) CXCR5(+) CD4(+) T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure

Jing He, Louis M Tsai, Yew A Leong, Xin Jack Hu, Cindy S Ma, Nina Chevalier, Xiaolin Sun, Kirsten Vandenberg, Steve Rockman, Yan Ding, Lei Zhu, Wei Wei, Changqi Wang, Alexander Karnowski, Gabrielle T Belz, Joanna R Ghali, Matthew C Cook, Sean Riminton, Andre Veillette, Pamela L Schwartzberg & 7 others Fabienne Mackay, Robert Brink, Stuart G Tangye, Carola G Vinuesa, Charles R Mackay, Zhan Guo Li, Di Yu

Research output: Contribution to journalArticleResearchpeer-review

295 Citations (Scopus)

Abstract

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 antibody 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.
Original languageEnglish
Pages (from-to)770 - 781
Number of pages12
JournalImmunity
Volume39
DOIs
Publication statusPublished - 2013

Cite this

He, Jing ; Tsai, Louis M ; Leong, Yew A ; Hu, Xin Jack ; Ma, Cindy S ; Chevalier, Nina ; Sun, Xiaolin ; Vandenberg, Kirsten ; Rockman, Steve ; Ding, Yan ; Zhu, Lei ; Wei, Wei ; Wang, Changqi ; Karnowski, Alexander ; Belz, Gabrielle T ; Ghali, Joanna R ; Cook, Matthew C ; Riminton, Sean ; Veillette, Andre ; Schwartzberg, Pamela L ; Mackay, Fabienne ; Brink, Robert ; Tangye, Stuart G ; Vinuesa, Carola G ; Mackay, Charles R ; Li, Zhan Guo ; Yu, Di. / Circulating precursor CCR7(lo)PD-1(hi) CXCR5(+) CD4(+) T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure. In: Immunity. 2013 ; Vol. 39. pp. 770 - 781.
@article{5f28a8f348224c3fafb3269aaad9ebda,
title = "Circulating precursor CCR7(lo)PD-1(hi) CXCR5(+) CD4(+) T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure",
abstract = "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 antibody 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.",
author = "Jing He and Tsai, {Louis M} and Leong, {Yew A} and Hu, {Xin Jack} and Ma, {Cindy S} and Nina Chevalier and Xiaolin Sun and Kirsten Vandenberg and Steve Rockman and Yan Ding and Lei Zhu and Wei Wei and Changqi Wang and Alexander Karnowski and Belz, {Gabrielle T} and Ghali, {Joanna R} and Cook, {Matthew C} and Sean Riminton and Andre Veillette and Schwartzberg, {Pamela L} and Fabienne Mackay and Robert Brink and Tangye, {Stuart G} and Vinuesa, {Carola G} and Mackay, {Charles R} and Li, {Zhan Guo} and Di Yu",
year = "2013",
doi = "10.1016/j.immuni.2013.09.007",
language = "English",
volume = "39",
pages = "770 -- 781",
journal = "Immunity",
issn = "1074-7613",
publisher = "Elsevier",

}

He, J, Tsai, LM, Leong, YA, Hu, XJ, Ma, CS, Chevalier, N, Sun, X, Vandenberg, K, Rockman, S, Ding, Y, Zhu, L, Wei, W, Wang, C, Karnowski, A, Belz, GT, Ghali, JR, Cook, MC, Riminton, S, Veillette, A, Schwartzberg, PL, Mackay, F, Brink, R, Tangye, SG, Vinuesa, CG, Mackay, CR, Li, ZG & Yu, D 2013, 'Circulating precursor CCR7(lo)PD-1(hi) CXCR5(+) CD4(+) T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure', Immunity, vol. 39, pp. 770 - 781. https://doi.org/10.1016/j.immuni.2013.09.007

Circulating precursor CCR7(lo)PD-1(hi) CXCR5(+) CD4(+) T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure. / He, Jing; Tsai, Louis M; Leong, Yew A; Hu, Xin Jack; Ma, Cindy S; Chevalier, Nina; Sun, Xiaolin; Vandenberg, Kirsten; Rockman, Steve; Ding, Yan; Zhu, Lei; Wei, Wei; Wang, Changqi; Karnowski, Alexander; Belz, Gabrielle T; Ghali, Joanna R; Cook, Matthew C; Riminton, Sean; Veillette, Andre; Schwartzberg, Pamela L; Mackay, Fabienne; Brink, Robert; Tangye, Stuart G; Vinuesa, Carola G; Mackay, Charles R; Li, Zhan Guo; Yu, Di.

In: Immunity, Vol. 39, 2013, p. 770 - 781.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Circulating precursor CCR7(lo)PD-1(hi) CXCR5(+) CD4(+) T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure

AU - He, Jing

AU - Tsai, Louis M

AU - Leong, Yew A

AU - Hu, Xin Jack

AU - Ma, Cindy S

AU - Chevalier, Nina

AU - Sun, Xiaolin

AU - Vandenberg, Kirsten

AU - Rockman, Steve

AU - Ding, Yan

AU - Zhu, Lei

AU - Wei, Wei

AU - Wang, Changqi

AU - Karnowski, Alexander

AU - Belz, Gabrielle T

AU - Ghali, Joanna R

AU - Cook, Matthew C

AU - Riminton, Sean

AU - Veillette, Andre

AU - Schwartzberg, Pamela L

AU - Mackay, Fabienne

AU - Brink, Robert

AU - Tangye, Stuart G

AU - Vinuesa, Carola G

AU - Mackay, Charles R

AU - Li, Zhan Guo

AU - Yu, Di

PY - 2013

Y1 - 2013

N2 - 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 antibody 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.

AB - 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 antibody 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.

UR - http://www.ncbi.nlm.nih.gov/pubmed/24138884

U2 - 10.1016/j.immuni.2013.09.007

DO - 10.1016/j.immuni.2013.09.007

M3 - Article

VL - 39

SP - 770

EP - 781

JO - Immunity

JF - Immunity

SN - 1074-7613

ER -