title: Differential B7-CD28 costimulatory requirements for stable and inflationary mouse cytomegalovirus-specific memory CD8 T cell populations.
abstract: CMV establishes a lifelong persistent infection, and viral immune-modulating strategies are important in facilitating this. A particularly diverse CD8 T cell response develops as a result of this host-virus détente, with the CMV-specific memory T cell pool displaying unique functions and phenotypes. To gain insight into the factors that regulate CMV-specific CD8 T cell responses, we examined the influence of the B7-CD28 costimulatory pathway on magnitude, kinetics, and phenotype. Initial expansion of mouse CMV-specific CD8 T cells that establish stable memory pools was severely lower in mice lacking B7-CD28 signaling, and the resulting memory levels also remained reduced during persistent/latent infection. In contrast, expansion of CD8 T cells that undergo memory inflation during chronic infection was less affected in the absence of B7-CD28 costimulatory signals, eventually reaching the levels seen in wild-type mice at later times. Regardless of their differential requirements for B7-CD28 signals, both stable and inflationary memory T cell populations showed normal cytotoxic capacity. These results reveal that B7-CD28 costimulation differentially regulates the magnitude and kinetics of the multifaceted CD8 T cell response that develops during CMV infection.
authors.affiliation: Laboratory of Cellular Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. R.Arens@lumc.nl
authors.forename: Ramon
authors.initials: R
authors.lastname: Arens
authors.forename: Andrea
authors.initials: A
authors.lastname: Loewendorf
authors.forename: Anke
authors.initials: A
authors.lastname: Redeker
authors.forename: Sophie
authors.initials: S
authors.lastname: Sierro
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
authors.forename: Chris A
authors.initials: CA
authors.lastname: Benedict
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Schoenberger
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics; D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051940:B7-2 Antigen / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018106:CD28 Antigens / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007156:Immunologic Memory / Q000235:genetics; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018146:Muromegalovirus / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D018984:Epitopes, T-Lymphocyte