IL-7 regulates basal homeostatic proliferation of antiviral CD4 +T cell memory

Derek C. Lenz, Sabine K. Kurz, Edward Lemmens, Stephen P. Schoenberger, Jonathan Sprent, Michael B.A. Oldstone, Dirk Homann

Research output: Contribution to journalArticlepeer-review

168 Scopus citations

Abstract

Heightened protection from infectious disease as conferred by vaccination or pathogen exposure relies on the effective generation and preservation of specific immunological memory. T cells are irreducibly required for the control of most viral infections, and maintenance of CD8+T cell memory is regulated by at least two cytokines, IL-7 and IL-15, which support survival (IL-7, IL-15) and basal homeostatic proliferation (IL-15) of specific CD8 + memory T cells (TM). In contrast, the factors governing the homeostasis of pathogen-specific CD4+TM remain at present unknown. Here, we used a physiologic in vivo model system for viral infection to delineate homeostatic features and mechanisms of antiviral CD4 +TM preservation in direct juxtaposition to CD8 +T cell memory. Basal homeostatic proliferation is comparable between specific CD4+ and CD8+TM and independent of immunodominant determinants and functional avidities but regulated in a tissue-specific fashion. IL-7, identified as the dominant cytokine, and IL-15, an accessory cytokine, regulate basal homeostatic proliferation and survival of antiviral CD4+TM. Interestingly, a role for these cytokines in regulation of CD4+T cell memory is not readily discernible in the generic "memory-phenotype" population, apparently a consequence of its heterogeneous composition. We also describe a prominent, nonredundant role for IL-7 in supporting basal homeostatic proliferation of CD8+TM. We propose that homeostatic control of antiviral CD4+ and CD8+ T cell memory is fundamentally similar and characterized by quantitative, rather than qualitative, differences.

Original languageEnglish
Pages (from-to)9357-9362
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number25
DOIs
StatePublished - 22 Jun 2004
Externally publishedYes

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