Regulatory roles of IL-10-producing human follicular T cells

Pablo F. Cañete; Rebecca A. Sweet; Paula Gonzalez-Figueroa; Ilenia Papa; Naganari Ohkura; Holly Bolton; Jonathan A. Roco; Marta Cuenca; Katharine J. Bassett; Ismail Sayin; Emma Barry; Angel Lopez; David H. Canaday; Michael Meyer-Hermann; Claudio Doglioni; Barbara Fazekas De St Groth; Shimon Sakaguchi; Matthew C. Cook; Carola G. Vinuesa

doi:10.1084/jem.20190493

Regulatory roles of IL-10-producing human follicular T cells

Pablo F. Cañete, Rebecca A. Sweet, Paula Gonzalez-Figueroa, Ilenia Papa, Naganari Ohkura, Holly Bolton, Jonathan A. Roco, Marta Cuenca, Katharine J. Bassett, Ismail Sayin, Emma Barry, Angel Lopez, David H. Canaday, Michael Meyer-Hermann, Claudio Doglioni, Barbara Fazekas De St Groth, Shimon Sakaguchi, Matthew C. Cook, Carola G. Vinuesa^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

70 Citations (Scopus)

Abstract

Mucosal lymphoid tissues such as human tonsil are colonized by bacteria and exposed to ingested and inhaled antigens, requiring tight regulation of immune responses. Antibody responses are regulated by follicular helper T (T_FH) cells and FOXP3⁺ follicular regulatory T (T_FR) cells. Here we describe a subset of human tonsillar follicular T cells identified by expression of T_FH markers and CD25 that are the main source of follicular T (T_F) cell-derived IL-10. Despite lack of FOXP3 expression, CD25⁺ T_F cells resemble T reg cells in high CTLA4 expression, low IL-2 production, and their ability to repress T cell proliferation. CD25⁺ T_F cell-derived IL-10 dampens induction of B cell class-switching to IgE. In children, circulating total IgE titers were inversely correlated with the frequencies of tonsil CD25⁺ T_F cells and IL-10-producing T_F cells but not with total T reg cells, T_FR, or IL-10-producing T cells. Thus, CD25⁺ T_F cells emerge as a subset with unique T and B cell regulatory activities that may help prevent atopy.

Original language	English
Pages (from-to)	1843-1856
Number of pages	14
Journal	Journal of Experimental Medicine
Volume	216
Issue number	8
DOIs	https://doi.org/10.1084/jem.20190493
Publication status	Published - 1 Aug 2019

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Cañete, P. F., Sweet, R. A., Gonzalez-Figueroa, P., Papa, I., Ohkura, N., Bolton, H., Roco, J. A., Cuenca, M., Bassett, K. J., Sayin, I., Barry, E., Lopez, A., Canaday, D. H., Meyer-Hermann, M., Doglioni, C., De St Groth, B. F., Sakaguchi, S., Cook, M. C., & Vinuesa, C. G. (2019). Regulatory roles of IL-10-producing human follicular T cells. Journal of Experimental Medicine, 216(8), 1843-1856. https://doi.org/10.1084/jem.20190493

@article{02b5fcbc59924d939c482dcd5c5ded6a,

title = "Regulatory roles of IL-10-producing human follicular T cells",

abstract = "Mucosal lymphoid tissues such as human tonsil are colonized by bacteria and exposed to ingested and inhaled antigens, requiring tight regulation of immune responses. Antibody responses are regulated by follicular helper T (TFH) cells and FOXP3+ follicular regulatory T (TFR) cells. Here we describe a subset of human tonsillar follicular T cells identified by expression of TFH markers and CD25 that are the main source of follicular T (TF) cell-derived IL-10. Despite lack of FOXP3 expression, CD25+ TF cells resemble T reg cells in high CTLA4 expression, low IL-2 production, and their ability to repress T cell proliferation. CD25+ TF cell-derived IL-10 dampens induction of B cell class-switching to IgE. In children, circulating total IgE titers were inversely correlated with the frequencies of tonsil CD25+ TF cells and IL-10-producing TF cells but not with total T reg cells, TFR, or IL-10-producing T cells. Thus, CD25+ TF cells emerge as a subset with unique T and B cell regulatory activities that may help prevent atopy.",

author = "Ca{\~n}ete, {Pablo F.} and Sweet, {Rebecca A.} and Paula Gonzalez-Figueroa and Ilenia Papa and Naganari Ohkura and Holly Bolton and Roco, {Jonathan A.} and Marta Cuenca and Bassett, {Katharine J.} and Ismail Sayin and Emma Barry and Angel Lopez and Canaday, {David H.} and Michael Meyer-Hermann and Claudio Doglioni and {De St Groth}, {Barbara Fazekas} and Shimon Sakaguchi and Cook, {Matthew C.} and Vinuesa, {Carola G.}",

note = "Publisher Copyright: {\textcopyright} 2019 Ca{\~n}ete et al.",

year = "2019",

month = aug,

day = "1",

doi = "10.1084/jem.20190493",

language = "English",

volume = "216",

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Cañete, PF, Sweet, RA, Gonzalez-Figueroa, P, Papa, I, Ohkura, N, Bolton, H, Roco, JA, Cuenca, M, Bassett, KJ, Sayin, I, Barry, E, Lopez, A, Canaday, DH, Meyer-Hermann, M, Doglioni, C, De St Groth, BF, Sakaguchi, S, Cook, MC & Vinuesa, CG 2019, 'Regulatory roles of IL-10-producing human follicular T cells', Journal of Experimental Medicine, vol. 216, no. 8, pp. 1843-1856. https://doi.org/10.1084/jem.20190493

TY - JOUR

T1 - Regulatory roles of IL-10-producing human follicular T cells

AU - Cañete, Pablo F.

AU - Sweet, Rebecca A.

AU - Gonzalez-Figueroa, Paula

AU - Papa, Ilenia

AU - Ohkura, Naganari

AU - Bolton, Holly

AU - Roco, Jonathan A.

AU - Cuenca, Marta

AU - Bassett, Katharine J.

AU - Sayin, Ismail

AU - Barry, Emma

AU - Lopez, Angel

AU - Canaday, David H.

AU - Meyer-Hermann, Michael

AU - Doglioni, Claudio

AU - De St Groth, Barbara Fazekas

AU - Sakaguchi, Shimon

AU - Cook, Matthew C.

AU - Vinuesa, Carola G.

PY - 2019/8/1

Y1 - 2019/8/1

N2 - Mucosal lymphoid tissues such as human tonsil are colonized by bacteria and exposed to ingested and inhaled antigens, requiring tight regulation of immune responses. Antibody responses are regulated by follicular helper T (TFH) cells and FOXP3+ follicular regulatory T (TFR) cells. Here we describe a subset of human tonsillar follicular T cells identified by expression of TFH markers and CD25 that are the main source of follicular T (TF) cell-derived IL-10. Despite lack of FOXP3 expression, CD25+ TF cells resemble T reg cells in high CTLA4 expression, low IL-2 production, and their ability to repress T cell proliferation. CD25+ TF cell-derived IL-10 dampens induction of B cell class-switching to IgE. In children, circulating total IgE titers were inversely correlated with the frequencies of tonsil CD25+ TF cells and IL-10-producing TF cells but not with total T reg cells, TFR, or IL-10-producing T cells. Thus, CD25+ TF cells emerge as a subset with unique T and B cell regulatory activities that may help prevent atopy.

AB - Mucosal lymphoid tissues such as human tonsil are colonized by bacteria and exposed to ingested and inhaled antigens, requiring tight regulation of immune responses. Antibody responses are regulated by follicular helper T (TFH) cells and FOXP3+ follicular regulatory T (TFR) cells. Here we describe a subset of human tonsillar follicular T cells identified by expression of TFH markers and CD25 that are the main source of follicular T (TF) cell-derived IL-10. Despite lack of FOXP3 expression, CD25+ TF cells resemble T reg cells in high CTLA4 expression, low IL-2 production, and their ability to repress T cell proliferation. CD25+ TF cell-derived IL-10 dampens induction of B cell class-switching to IgE. In children, circulating total IgE titers were inversely correlated with the frequencies of tonsil CD25+ TF cells and IL-10-producing TF cells but not with total T reg cells, TFR, or IL-10-producing T cells. Thus, CD25+ TF cells emerge as a subset with unique T and B cell regulatory activities that may help prevent atopy.

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U2 - 10.1084/jem.20190493

DO - 10.1084/jem.20190493

M3 - Article

SN - 0022-1007

VL - 216

SP - 1843

EP - 1856

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

IS - 8

ER -

Regulatory roles of IL-10-producing human follicular T cells

Abstract

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