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The Journal of Immunology, 2001, 167: 5565-5573.
Copyright © 2001 by The American Association of Immunologists

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

M. Suresh2,*,{ddagger}, Jason K. Whitmire2,*, Laurie E. Harrington*, Christian P. Larsen{dagger}, Thomas C. Pearson{dagger}, John D. Altman* and Rafi Ahmed3,*

* Emory Vaccine Center and Department of Microbiology and Immunology and {dagger} Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322; and {ddagger} Department of Pathobiological Sciences, University of Wisconsin, Madison, WI 53706

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 ~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 ~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.




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