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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Heit, A; Schmitz, F; Gerdts, S; Flach, B; Moore, MS; Perkins, JA; Robins, HS; Aderem, A; Spearman, P; Tomaras, GD; De Rosa, SC; McElrath, MJ

Published Date

  • July 3, 2017

Published In

Volume / Issue

  • 214 / 7

Start / End Page

  • 2139 - 2152

PubMed ID

  • 28637884

Pubmed Central ID

  • 28637884

Electronic International Standard Serial Number (EISSN)

  • 1540-9538

Digital Object Identifier (DOI)

  • 10.1084/jem.20161794

Language

  • eng

Conference Location

  • United States