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The Journal of Immunology, 2001, 167: 132-139.
Copyright © 2001 by The American Association of Immunologists

Enhancement of CD8+ T Cell Responses by ICOS/B7h Costimulation1

Jeffrey J. Wallin, Linda Liang, Anastasia Bakardjiev and William C. Sha2

Immunology Division, Cancer Research Laboratory, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720

Although the recently identified ICOS/B7h costimulatory counterreceptors are critical regulators of CD4+ T cell responses, their ability to regulate CD8+ responses is unclear. Here we report using a tumor-rejection model that ectopic B7h expression can costimulate rejection by CD8+ T cells in the absence of CD4+ T cells. Although responses of naive T cells were significantly augmented by priming with B7h, B7h was surprisingly effective in mobilizing recall responses of adoptively transferred T cells. To explore why secondary responses of CD8+ T cells were particularly enhanced by B7h, kinetics of ICOS up-regulation, proliferative responses, and cytokine production were compared from both naive and rechallenged 2C-transgenic T cells costimulated in vitro. Although B7h costimulated proliferative responses from both CD8+ populations, rechallenged cells were preferentially costimulated for IL-2 and IFN-{gamma} production. These results indicate that ICOS/B7h counterreceptors likely function in vivo to enhance secondary responses by CD8+ T cells.




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