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CD81 and CD28 Costimulate T Cells Through Distinct Pathways¹

Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037

We have examined the role of CD81 in the activation of murine splenic ß T cells. Expression of the CD81 molecule on T cells increases following activation, raising the possibility of a role for this molecule in progression of the activation process. Using an in vitro costimulation assay, we show that CD81 can function as a costimulatory molecule on both CD4⁺ and CD8⁺ T cells. This costimulation functions independently of CD28, and unlike costimulation through CD28, is susceptible to inhibition by cyclosporin A. Strikingly, the pattern of cytokine production elicited by costimulation via CD81 is unique. IL-2 production was not up-regulated, whereas both IFN- and TNF- expression significantly increased. Together our results demonstrate an alternate pathway for costimulation of T cell activation mediated by CD81.

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