Differential B7-CD28 costimulatory requirements for stable and inflationary mouse cytomegalovirus-specific memory CD8 T cell populations.

Journal article

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: Arens, R; Loewendorf, A; Redeker, A; Sierro, S; Boon, L

• Publication status: Published
• Journal: Journal of Immunology
• Volume: 186
• Issue: 7
• Pages: 3874-3881
• Publication date: 2011-04-01
• DOI: 10.4049/jimmunol.1003231
• EISSN: 1550-6606
• ISSN: 0022-1767
• Language: English
• Keywords: Immunologic Memory; Antigens, CD28; Mice, Inbred BALB C; Cytotoxicity, Immunologic; Epitopes, T-Lymphocyte; Antigens, CD86; Muromegalovirus; Antigens, CD80; Mice, Inbred C57BL; Adaptive Immunity; Mice; Animals; Lymphopenia; Cell Differentiation; Mice, Transgenic; CD8-Positive T-Lymphocytes; Herpesviridae Infections; Signal Transduction; Mice, Knockout