title: IL-7 regulates basal homeostatic proliferation of antiviral CD4+T cell memory.
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 (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.
authors.affiliation: Departments of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Derek C
authors.initials: DC
authors.lastname: Lenz
authors.forename: Sabine K
authors.initials: SK
authors.lastname: Kurz
authors.forename: Edward
authors.initials: E
authors.lastname: Lemmens
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Schoenberger
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sprent
authors.forename: Michael B A
authors.initials: MB
authors.lastname: Oldstone
authors.forename: Dirk
authors.initials: D
authors.lastname: Homann
mesh_terms: D000818:Animals; D000915:Antibody Affinity / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002455:Cell Division; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D015851:Interleukin-7 / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D014780:Viruses / Q000276:immunology*
chemical_list: D015851:Interleukin-7