Successive annual influenza vaccination induces a recurrent oligoclonotypic memory response in circulating T follicular helper cells.


Journal Article

T follicular helper (Tfh) CD4 cells are crucial providers of B cell help during adaptive immune responses. A circulating population of CD4 T cells, termed cTfh, have similarity to lymphoid Tfh, can provide B cell help, and responded to influenza vaccination. However, it is unclear whether human vaccination-induced cTfh respond in an antigen-specific manner and whether they form long-lasting memory. Here, we identified a cTfh population that expressed multiple T cell activation markers and could be readily identified by coexpression of ICOS and CD38. This subset expressed more Bcl-6, c-Maf, and IL-21 than other blood CD4 subsets. Influenza vaccination induced a strong response in the ICOS+CD38+ cTfh at day 7, and this population included hemagglutinin-specific cells by tetramer staining and antigen-stimulated Activation Induced Marker (AIM) expression. Moreover, TCRB sequencing identified a clonal response in ICOS+CD38+ cTfh that correlated strongly with the increased circulating ICOS+CD38+ cTfh frequency and the circulating plasmablast response. In subjects who received successive annual vaccinations, a recurrent oligoclonal response was identified in the ICOS+CD38+ cTfh subset at 7 days after every vaccination. These oligoclonal responses in ICOS+CD38+ cTfh after vaccination persisted in the ICOS-CD38- cTfh repertoire in subsequent years, suggesting clonal maintenance in a memory reservoir in the more-stable ICOS-CD38- cTfh subset. These data highlight the antigen-specificity, lineage relationships and memory properties of human cTfh responses to vaccination, providing new avenues for tracking and monitoring cTfh responses during infection and vaccination in humans.

Full Text

Duke Authors

Cited Authors

  • Herati, RS; Muselman, A; Vella, L; Bengsch, B; Parkhouse, K; Del Alcazar, D; Kotzin, J; Doyle, SA; Tebas, P; Hensley, SE; Su, LF; Schmader, KE; Wherry, EJ

Published Date

  • February 2017

Published In

Volume / Issue

  • 2 / 8

PubMed ID

  • 28620653

Pubmed Central ID

  • 28620653

International Standard Serial Number (ISSN)

  • 2470-9468

Digital Object Identifier (DOI)

  • 10.1126/sciimmunol.aag2152


  • eng

Conference Location

  • United States