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

First Author  Lenz DC Year  2004
Journal  Proc Natl Acad Sci U S A Volume  101
Issue  25 Pages  9357-62
PubMed ID  15197277 Mgi Jnum  J:91400
Mgi Id  MGI:3047007 Doi  10.1073/pnas.0400640101
Citation  Lenz DC, et al. (2004) IL-7 regulates basal homeostatic proliferation of antiviral CD4+T cell memory. Proc Natl Acad Sci U S A 101(25):9357-62
abstractText  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 (T(M)). In contrast, the factors governing the homeostasis of pathogen-specific CD4(+)T(M) 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(+)T(M) preservation in direct juxtaposition to CD8(+)T cell memory. Basal homeostatic proliferation is comparable between specific CD4(+) and CD8(+)T(M) 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(+)T(M). 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(+)T(M). We propose that homeostatic control of antiviral CD4(+) and CD8(+) T cell memory is fundamentally similar and characterized by quantitative, rather than qualitative, differences.
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