title: CD4+ T cell help has an epitope-dependent impact on CD8+ T cell memory inflation during murine cytomegalovirus infection.
abstract: Murine CMV (MCMV) establishes a systemic, low-level persistent infection resulting in the accumulation of CD8(+) T cells specific for a subset of viral epitopes, a process called memory inflation. Although replicating virus is rarely detected in chronically infected C57BL/6 mice, these inflationary cells display a phenotype suggestive of repeated Ag stimulation, and they remain functional. CD4(+) T cells have been implicated in maintaining the function and/or number of CD8(+) T cells in other chronic infections. Moreover, CD4(+) T cells are essential for complete control of MCMV. Thus, we wondered whether CD4(+) T cell deficiency would result in impaired MCMV-specific CD8(+) T cell responses. Here we show that CD4(+) T cell deficiency had an epitope-specific impact on CD8(+) T cell memory inflation. Of the three codominant T cell responses during chronic infection, only accumulation of the late-appearing IE3-specific CD8(+) T cells was substantially impaired in CD4(+) T cell-deficient mice. Moreover, the increased viral activity did not drive increased CD8(+) T cell division or substantial dysfunction in any MCMV-specific population that we studied. These data show that CD4(+) T cell help is needed for inflation of a response that develops only during chronic infection but is otherwise dispensable for the steady state maintenance and function of MCMV-specific CD8(+) T cells.
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, OR 97239, USA. snydechr@ohsu.edu
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Snyder
authors.forename: Andrea
authors.initials: A
authors.lastname: Loewendorf
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Bonnett
authors.forename: Michael
authors.initials: M
authors.lastname: Croft
authors.forename: Chris A
authors.initials: CA
authors.lastname: Benedict
authors.forename: Ann B
authors.initials: AB
authors.lastname: Hill
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D006566:Herpesviridae Infections / Q000276:immunology*; D017874:Immediate-Early Proteins / Q000276:immunology; D007156:Immunologic Memory; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D000939:Epitopes; C088646:IE3 protein, cytomegalovirus; D017874:Immediate-Early Proteins
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