Abstract
CD8+ Tcells mediate acute rejection of allografts, which threatens the long-term survival of transplanted organs. Using MHC class I tetramers, we find that allogeneic CD8+ Tcells are present at an elevated naive precursor frequency relative to other epitopes, only modestly increase in number after grafting, and maintain high Tcell receptor diversity throughout the immune response. While antigen-specific effector CD8+ Tcells poorly express the canonical effector marker KLRG-1, expression of the activated glycoform of CD43 defines potent effectors after transplantation. Activated CD43+ effector Tcells maintain high expression of the coreceptor induced T cell costimulator (ICOS) in the presence of CTLA-4 immunoglobulin (Ig), and dual CTLA-4 Ig/anti-ICOS treatment prolongs graft survival. These data demonstrate that graft-specific CD8+ Tcells have a distinct response profile relative to anti-pathogen CD8+ Tcells and that CD43 and ICOS are critical surface receptors that define potent effector CD8+ Tcell populations that form after transplantation.
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