Stability and function of secondary Th1 memory cells are dependent on the nature of the secondary stimulus

Chulwoo Kim, David C. Jay, Matthew A. Williams

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Following acute infection in some mouse models, CD4+ memory T cells steadily decline over time. Conversely, in humans, CD4+ memory T cells can be maintained for many years at levels similar to CD8+ T cells. Because we previously observed that the longevity of Th1 memory cell survival corresponded to their functional avidity, we hypothesized that secondary challenge, which enriches for high functional avidity Th1 responders, would result in more stable Th1 memory populations. We found that following a heterologous secondary challenge, Th1 memory cells were maintained at stable levels compared with primary Th1 memory cells, showing little to no decline after day 75 postinfection. The improved stability of secondary Th1 memory T cells corresponded to enhanced homeostatic turnover; enhanced trafficking of effector memory Th1 cells to tissue sites of infection, such as the liver; and acquisition or maintenance of high functional avidity following secondary challenge. Conversely, a weaker homologous rechallenge failed to induce a stable secondary Th1 memory population. Additionally, homologous secondary challenge resulted in a transient loss of functional avidity by Th1 memory cells recruited into the secondary response. Our findings suggest that the longevity of Th1 memory T cells is dependent, at least in part, on the combined effects of primary and secondary Ag-driven differentiation. Furthermore, they demonstrate that the quality of the secondary challenge can have profound effects on the longevity and function of the ensuing secondary Th1 memory population.

Original languageEnglish
Pages (from-to)2348-2355
Number of pages8
JournalJournal of Immunology
Volume189
Issue number5
DOIs
Publication statusPublished - 2012 Sep 1
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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