title: Role of CD28-B7 interactions in generation and maintenance of CD8 T cell memory.
abstract: Although the role of CD28-B7 interaction in the activation of naive T cells is well established, its importance in the generation and maintenance of T cell memory is not well understood. In this study, we examined the requirement for CD28-B7 interactions in primary T cell activation and immune memory. Ag-specific CD8 T cell responses were compared between wild-type (+/+) and CD28-deficient (CD28(-/-)) mice following an acute infection with lymphocytic choriomeningitis virus (LCMV). During the primary response, there was a substantial activation and expansion of LCMV-specific CD8 T cells in both +/+ and CD28(-/-) mice. However, the magnitude of the primary CD8 T cell response to both dominant and subdominant LCMV CTL epitopes was approximately 2- to 3-fold lower in CD28(-/-) mice compared with +/+ mice; the lack of CD28-mediated costimulation did not lead to preferential suppression of CD8 T cell responses to the weaker subdominant epitopes. As seen in CD28(-/-) mice, blockade of B7-mediated costimulation by CTLA4-Ig treatment of +/+ mice also resulted in a 2-fold reduction in the anti-LCMV CD8 T cell responses. Loss of CD28/B7 interactions did not significantly affect the generation and maintenance of CD8 T cell memory; the magnitude of CD8 T cell memory was approximately 2-fold lower in CD28(-/-) mice as compared with +/+ mice. Further, in CD28(-/-) mice, LCMV-specific memory CD8 T cells showed normal homeostatic proliferation in vivo and also conferred protective immunity. Therefore, CD28 signaling is not necessary for the proliferative renewal and maintenance of memory CD8 T cells.
authors.affiliation: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: M
authors.initials: M
authors.lastname: Suresh
authors.forename: J K
authors.initials: JK
authors.lastname: Whitmire
authors.forename: L E
authors.initials: LE
authors.lastname: Harrington
authors.forename: C P
authors.initials: CP
authors.lastname: Larsen
authors.forename: T C
authors.initials: TC
authors.lastname: Pearson
authors.forename: J D
authors.initials: JD
authors.lastname: Altman
authors.forename: R
authors.initials: R
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D001117:Arenaviridae Infections / Q000276:immunology; D018122:B7-1 Antigen / Q000378:metabolism / Q000502:physiology*; D018106:CD28 Antigens / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D006706:Homeostasis; D016056:Immunodominant Epitopes / Q000276:immunology; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D018122:B7-1 Antigen; D018106:CD28 Antigens; D016056:Immunodominant Epitopes