Role of CD28-B7 interactions in generation and maintenance of CD8 T cell memory

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 require ment for CD28-B7 interactions in primary T cell activation and immune memor y. Ag-specific CD8 T cell responses were compared between wild-type (+/+) a nd CD28-deficient (CD28(-/-)) mice following an acute infection with lympho cytic choriomeningitis virus (LCMV). During the primary response, there was a substantial activation and expansion of LCMV-specific CD8 T cells in bot h +/+ and CD28(-/-) mice. However, the magnitude of the primary CD8 T cell response to both dominant and subdominant LOW CTL epitopes was similar to2- 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 ce ll responses to the weaker subdominant epitopes. As seen in CD28(-/-) mice, blockade of B7-mediated costimulation by CTLA4-Ig treatment of +/+ mice al so resulted in a 2-fold reduction in the anti-LCMV CD8 T cell responses. Lo ss 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 si milar to2-fold lower in CD28(-/-) mice as compared with +/+ mice. Further, in CD28(-/-) mice, LCMV-specific memory CD8 T cells showed normal homeostat ic proliferation in vivo and also conferred protective immunity. Therefore, CD28 signaling is not necessary for the proliferative renewal and maintena nce of memory CD8 T cells.