Differential regulation of antiviral T-cell immunity results in stable CD8+ but declining CD4+ T-cell memory

Dirk Homann, Luc Teyton, Michael B.A. Oldstone

Research output: Contribution to journalArticlepeer-review

500 Scopus citations

Abstract

Emerging evidence indicates that CD8+ and CD4+ T-cell immunity is differentially regulated. Here we have delineated differences and commonalities among antiviral T-cell responses by enumeration and functional profiling of eight specific CD8+ and CD4+ T-cell populations during primary, memory and recall responses. A high degree of coordinate regulation among all specific T-cell populations stood out against an approximately 20-fold lower peak expansion and prolonged contraction phase of specific CD4+ T-cell populations. Surprisingly, although CD8+ T-cell memory was stably maintained for life, levels of specific CD4+ memory T cells gradually declined. However, this decay, which seemed to result from less efficient rescue from apoptosis, did not affect functionality of surviving virus-specific CD4+ T cells. Our results indicate that CD4+ T-cell memory might become limiting under physiological conditions and that conditions precipitating CD4+ T-cell loss might compromise protective immunity even in the presence of unimpaired CD8+ T-cell responses.

Original languageEnglish
Pages (from-to)913-919
Number of pages7
JournalNature Medicine
Volume7
Issue number8
DOIs
StatePublished - 2001
Externally publishedYes

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