title: Differential T cell responses to residual viral antigen prolong CD4+ T cell contraction following the resolution of infection.
abstract: The contraction phase of the T cell response is a poorly understood period after the resolution of infection when virus-specific effector cells decline in number and memory cells emerge with increased frequencies. CD8(+) T cells plummet in number and quickly reach stable levels of memory following acute lymphocytic choriomeningitis virus infection in mice. In contrast, virus-specific CD4(+) T cells gradually decrease in number and reach homeostatic levels only after many weeks. In this study, we provide evidence that MHCII-restricted viral Ag persists during the contraction phase following this prototypical acute virus infection. We evaluated whether the residual Ag affected the cell division and number of virus-specific naive and memory CD4(+) T cells and CD8(+) T cells. We found that naive CD4(+) T cells underwent cell division and accumulated in response to residual viral Ag for >2 mo after the eradication of infectious virus. Surprisingly, memory CD4(+) T cells did not undergo cell division in response to the lingering Ag, despite their heightened capacity to recognize Ag and make cytokine. In contrast to CD4(+) T cells, CD8(+) T cells did not undergo cell division in response to the residual Ag. Thus, CD8(+) T cells ceased division within days after the infection was resolved, indicating that CD8(+) T cell responses are tightly linked to endogenous processing of de novo synthesized virus protein. Our data suggest that residual viral Ag delays the contraction of CD4(+) T cell responses by recruiting new populations of CD4(+) T cells.
authors.affiliation: Department of Genetics, University of North Carolina School of Medicine, Chapel Hill, NC 27599;
authors.forename: Ichiro
authors.initials: I
authors.lastname: Misumi
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Alirezaei
authors.forename: Boreth
authors.initials: B
authors.lastname: Eam
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Su
authors.forename: J Lindsay
authors.initials: JL
authors.lastname: Whitton
authors.forename: Jason K
authors.initials: JK
authors.lastname: Whitmire
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D049109:Cell Proliferation; D002478:Cells, Cultured; D045142:Cross-Priming; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011485:Protein Binding
chemical_list: D000949:Histocompatibility Antigens Class II