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  • Title: Abrogation of functional selectin-ligand expression reduces migration of pathogenic CD8+ T cells into heart.
    Author: Cai YH, Alvarez A, Alcaide P, Duramad P, Lim YC, Jarolim P, Lowe JB, Luscinskas FW, Lichtman AH.
    Journal: J Immunol; 2006 Jun 01; 176(11):6568-75. PubMed ID: 16709814.
    Abstract:
    CD8+ T cells are involved in autoimmune and infectious myocarditis and cardiac allograft rejection. The role of selectins in cardiac recruitment of CD8+ T cells is not understood. In this study, the contribution of T cell selectin ligands to effector CD8+ T cell recruitment into the heart was examined using a model of myocarditis, which depends on transfer of OVA peptide-specific CD8+ T cells (OT-I) into mice (CMy-mOva) that express OVA in the heart. alpha-(1,3)-Fucosyltransferase (FucT)-VII-deficient OT-I cells displayed over a 95% reduction in their ability to interact with P-selectin under flow conditions in vitro, compared with wild-type OT-I cells. Interaction of FucT-VII-deficient OT-I cells with E-selectin was reduced approximately 50%. FucT-VII-deficient OT-I cells were also less efficiently recruited into a dermal site of Ag and adjuvant injection. Significantly, FucT-VII-deficient OT-I cells were also impaired in their ability to migrate into CMy-mOva hearts, compared with wild-type OT-I cells. Transfer of FucT-VII-deficient T cells caused less severe early myocarditis and myocyte damage than transfer of wild-type T cells. Combined FucT-IV/VII-deficient OT-I cells displayed a more profound reduction in E-selectin interactions in vitro compared with FucT-VII-deficient T cells, and the FucT-IV/VII-deficient T cells also showed less early recruitment and pathogenicity in the CMy-mOva myocarditis model. These results identify a prominent role for selectin ligands in contributing to effector CD8+ T cell recruitment into the myocardium and indicate that selectin-dependent T cell recruitment is relevant to other tissues besides the skin.
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