Role of CD28-B7 Interactions in Generation and Maintenance of CD8 T Cell Memory

• Published in: The Journal of immunology (1950) 2001-11, Vol.167 (10), p.5565-5573
• Main Authors: Suresh, M, Whitmire, Jason K, Harrington, Laurie E, Larsen, Christian P, Pearson, Thomas C, Altman, John D, Ahmed, Rafi
• Format: Article
• Language: English
• Subjects: AB7 antigen; Animals; Antigens, Viral - immunology; Arenaviridae Infections - immunology; B7-1 Antigen - metabolism; B7-1 Antigen - physiology; CD28 antigen; CD28 Antigens - genetics; CD28 Antigens - metabolism; CD28 Antigens - physiology; CD8 antigen; Cells, Cultured; Cytotoxicity Tests, Immunologic; Homeostasis; Immunodominant Epitopes - immunology; Immunologic Memory; Lymphocyte Activation; Lymphocytic choriomeningitis virus - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; T-Lymphocytes, Cytotoxic - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.10.5565

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.