title: Memory generation and maintenance of CD8+ T cell function during viral persistence.
abstract: During infection with viruses that establish latency, the immune system needs to maintain lifelong control of the infectious agent in the presence of persistent Ag. By using a gamma-herpesvirus (gammaHV) infection model, we demonstrate that a small number of virus-specific central-memory CD8+ T cells develop early during infection, and that virus-specific CD8+T cells maintain functional and protective capacities during chronic infection despite low-level Ag persistence. During the primary immune response, we show generation of CD8+ memory T cell precursors expressing lymphoid homing molecules (CCR7, L-selectin) and homeostatic cytokine receptors (IL-7alpha, IL-2/IL-15beta). During long-term persistent infection, central-memory cells constitute 20-50% of the virus-specific CD8+ T cell population and maintain the expression of L-selectin, CCR7, and IL-7R molecules. Functional analyses demonstrate that during viral persistence: 1) CD8+ T cells maintain TCR affinity for peptide/MHC complexes, 2) the functional avidity of CD8+ T cells measured as the capacity to produce IFN-gamma is preserved intact, and 3) virus-specific CD8+ T cells have in vivo killing capacity. Next, we demonstrate that at 8 mo post-virus inoculation, long-term CD8+ T cells are capable of mediating a protective recall response against the establishment of gammaHV68 splenic latency. These observations provide evidence that functional CD8+ memory T cells can be generated and maintained during low-load gammaHV68 persistence.
authors.affiliation: Center for Vaccines and Immunity, Columbus Children's Research Institute, Columbus, OH 43205, USA.
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: Cush
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Anderson
authors.forename: David H
authors.initials: DH
authors.lastname: Ravneberg
authors.forename: Janet L
authors.initials: JL
authors.lastname: Weslow-Schmidt
authors.forename: Emilio
authors.initials: E
authors.lastname: Flaño
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D018142:Gammaherpesvirinae / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology / Q000473:pathology; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics; D019562:Viral Load; D017735:Virus Latency / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell; D018121:Receptors, Cytokine