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Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756
Memory CD8+ T cell responses have been considered to be independent of CD80/CD86-CD28 costimulation. However, recall responses are often severely blunted in CD28–/– mice. Whether this impairment represents a requirement for CD28 costimulation for proper memory CD8+ T cell development or a requirement during the recall response is unknown. Furthermore, how CD28 costimulation affects the phenotype and function of memory CD8+ T cells has not been characterized in detail. In this study, we investigate these questions by studying the role of the CD28 costimulatory pathway in memory CD8+ T cell responses to acute and persistent DNA virus infections. Memory CD8+ T cells against vaccinia virus (VV) infection which develop without CD28 costimulation exhibit lower expression of differentiation markers CD27 and CD122 (IL-15Rβ). These memory CD8+ T cells also fail to produce IL-2. Our data indicate that for an optimal recall response, CD28 costimulation is required both for T cell priming and also during the recall response. Similar requirements were observed for memory CD8+ T cell responses during persistent infection with murine gammaherpesvirus 68 (MHV-68) infection, indicating CD28 may play the same role in both acute and persistent infections. Finally, we show deficits in the recall response are restored by IL-2 signaling during recall, but not during priming. The data presented show that CD28 costimulation not only controls the magnitude of the primary response but also affects development of memory CD8+ T cells and is required during the recall response in addition to initial T cell priming.
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1 This work was supported by National Institutes of Health Grant CA103642.
2 Address correspondence and reprint requests to Dr. Edward J. Usherwood, Department of Microbiology and Immunology, 1 Medical Center Drive, Darmouth Medical School, Lebanon, NH 03756. E-mail address: edward.j.usherwood{at}dartmouth.edu
3 Abbreviations used in this paper: LCMV, lymphocytic choriomeningitis virus; MHV-68, murine gammaherpesvirus 68; VV-WR, vaccinia virus Western Reserve; i.n., intranasal; rVV, recombinant VV; p.i., postinfection; mIL-2, murine IL-2; BM, bone marrow; R-IgG, rat IgG.
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