Abrogation of functional selectin-ligand expression reduces migration of pathogenic CD8+ T cells into heart

J Immunol. 2006 Jun 1;176(11):6568-75. doi: 10.4049/jimmunol.176.11.6568.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology*
  • CD8-Positive T-Lymphocytes / transplantation
  • Cell Communication / genetics
  • Cell Communication / immunology
  • Cell Migration Inhibition*
  • Cell Movement / genetics
  • Cell Movement / immunology*
  • Cells, Cultured
  • E-Selectin / biosynthesis
  • E-Selectin / metabolism*
  • E-Selectin / physiology
  • Fucosyltransferases / deficiency
  • Fucosyltransferases / genetics
  • Fucosyltransferases / metabolism
  • Ligands
  • Lymphocyte Activation / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Myocarditis / immunology
  • Myocarditis / pathology*
  • Myocarditis / prevention & control
  • P-Selectin / biosynthesis
  • P-Selectin / metabolism*
  • P-Selectin / physiology
  • Skin / cytology
  • Skin / immunology

Substances

  • E-Selectin
  • Ligands
  • P-Selectin
  • FUT7 protein, human
  • Fucosyltransferases