期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：25
页码：9357-9362
DOI：10.1073/pnas.0400640101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
