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

A Heit, F Schmitz, S Gerdts, B Flach… - Journal of Experimental …, 2017 - rupress.org
A Heit, F Schmitz, S Gerdts, B Flach, MS Moore, JA Perkins, HS Robins, A Aderem
Journal of Experimental Medicine, 2017rupress.org
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 …
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.
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