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Vaccination establishes clonal relatives of germinal center T cells in the blood of humans.


ABSTRACT: Germinal center T follicular helper cells (GCTfh) in lymphatic tissue are critical for B cell differentiation and protective antibody induction, but whether GCTfh establish clonal derivatives as circulating memory T cells is less understood. Here, we used markers expressed on GCTfh, CXCR5, PD1, and ICOS, to identify potential circulating CXCR5+CD4+ Tfh-like cells (cTfh) in humans, and investigated their functional phenotypes, diversity, and ontogeny in paired donor blood and tonsils, and in blood after vaccination. Based on T cell receptor repertoire analysis, we found that PD-1-expressing cTfh and tonsillar GCTfh cells were clonally related. Furthermore, an activated, antigen-specific PD1+ICOS+ cTfh subset clonally expanded after booster immunization whose frequencies correlated with vaccine-specific serum IgG; these phenotypically resembled GCTfh, and were clonally related to a resting PD1+ICOS- CD4+ memory T cell subset. Thus, we postulate that vaccination establishes clonal relatives of GCTfh within the circulating memory CD4+CXCR5+PD1+ T cell pool that expand upon reencounter of their cognate antigen.

SUBMITTER: Heit A 

PROVIDER: S-EPMC5502430 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Vaccination establishes clonal relatives of germinal center T cells in the blood of humans.

Heit Antje A   Schmitz Frank F   Gerdts Sarah S   Flach Britta B   Moore Miranda S MS   Perkins Jonathan A JA   Robins Harlan S HS   Aderem Alan A   Spearman Paul P   Tomaras Georgia D GD   De Rosa Stephen C SC   McElrath M Juliana MJ  

The Journal of experimental medicine 20170621 7


Germinal center T follicular helper cells (GCTfh) in lymphatic tissue are critical for B cell differentiation and protective antibody induction, but whether GCTfh establish clonal derivatives as circulating memory T cells is less understood. Here, we used markers expressed on GCTfh, CXCR5, PD1, and ICOS, to identify potential circulating CXCR5<sup>+</sup>CD4<sup>+</sup> Tfh-like cells (cTfh) in humans, and investigated their functional phenotypes, diversity, and ontogeny in paired donor blood an  ...[more]

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