The nature of the lymphopenic environment dictates protective function of homeostatic-memory CD8+ T cells

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A functional memory T cell pool is critical for resistance to pathogen reinfection. Lymphopenia produces memory-like CD8+ T cells through homeostatic proliferation, and such "HP-memory" cells can control lethal bacterial infections similarly to conventional, antigen-experienced, memory T cells. These 2 pathways for memory T cell generation are quite distinct. We show here, however, that similar factors are required for production of protective memory CD8 T cells via both homeostatic and conventional pathways. Induction of protective HP-memory CD8 T cells requires CD4+ T cell "help," which we show is antigen nonspecific yet requires CD40L-CD40 interactions with host cells. The functional competence of HP-memory CD8 T cells also requires release of endogenous bacterial components (which follows irradiation-induced lymphopenia), potentially mimicking the role of adjuvants in conventional immune responses. Lymphopenic environments lacking these key factors support similar CD8 T cell homeostatic proliferation and the acquisition of memory phenotype, yet the HP-memory cells generated are defective in pathogen elimination. These findings suggest unexpected parallels in the requirements for generating protective memory CD8 T cells by distinct pathways, and they suggest ways to bolster immune competence during recovery from lymphopenia.

Original languageEnglish (US)
Pages (from-to)18484-18489
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number47
StatePublished - Nov 25 2008


  • CD4 T cells
  • Homeostasis
  • Host defense
  • Lymphopenia


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