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Follicular regulatory T cells control humoral and allergic immunity by restraining early B cell responses.


ABSTRACT: Follicular regulatory T (TFR) cells have specialized roles in modulating follicular helper T (TFH) cell activation of B cells. However, the precise role of TFR cells in controlling antibody responses to foreign antigens and autoantigens in vivo is still unclear due to a lack of specific tools. A TFR cell-deleter mouse was developed that selectively deletes TFR cells, facilitating temporal studies. TFR cells were found to regulate early, but not late, germinal center (GC) responses to control antigen-specific antibody and B cell memory. Deletion of TFR cells also resulted in increased self-reactive immunoglobulin (Ig) G and IgE. The increased IgE levels led us to interrogate the role of TFR cells in house dust mite models. TFR cells were found to control TFH13 cell-induced IgE. In vivo, loss of TFR cells increased house-dust-mite-specific IgE and lung inflammation. Thus, TFR cells control IgG and IgE responses to vaccines, allergens and autoantigens, and exert critical immunoregulatory functions before GC formation.

SUBMITTER: Clement RL 

PROVIDER: S-EPMC6754271 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Follicular regulatory T cells control humoral and allergic immunity by restraining early B cell responses.

Clement Rachel L RL   Daccache Joe J   Mohammed Mostafa T MT   Diallo Alos A   Blazar Bruce R BR   Kuchroo Vijay K VK   Lovitch Scott B SB   Sharpe Arlene H AH   Sage Peter T PT  

Nature immunology 20190902 10


Follicular regulatory T (T<sub>FR</sub>) cells have specialized roles in modulating follicular helper T (T<sub>FH</sub>) cell activation of B cells. However, the precise role of T<sub>FR</sub> cells in controlling antibody responses to foreign antigens and autoantigens in vivo is still unclear due to a lack of specific tools. A T<sub>FR</sub> cell-deleter mouse was developed that selectively deletes T<sub>FR</sub> cells, facilitating temporal studies. T<sub>FR</sub> cells were found to regulate  ...[more]

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