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Blood, 15 April 2004, Vol. 103, No. 8, pp. 3111-3116.
Prepublished online as a Blood First Edition Paper on December 24, 2003; DOI 10.1182/blood-2003-08-2717.
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IMMUNOBIOLOGY
Cognate recognition of the endothelium induces HY-specific CD8+ T-lymphocyte transendothelial migration (diapedesis) in vivo
Federica M. Marelli-Berg,
Martha J. James,
John Dangerfield,
Julian Dyson,
Maggie Millrain,
Diane Scott,
Elizabeth Simpson,
Sussan Nourshargh, and
Robert I. Lechler
From the Department of Immunology, Division of Medicine, Imperial College London; the Cardiovascular Medicine Unit, Hammersmith Hospital Campus, Imperial College London, London, United Kingdom; and Transplantation Biology, MRC Clinical Sciences Centre, London, United Kingdom.
The physiologic significance of MHC-peptide complex presentation by endothelial cells (ECs) to trafficking T lymphocytes remains unresolved. On the basis of our observation that cognate recognition of ECs enhanced transendothelial migration of antigen-specific T lymphocytes in vitro, we have proposed that by displaying antigenic peptides from the underlying tissue, ECs promote the recruitment of antigen-specific T cells. In this study, we have tested this hypothesis by comparing the trafficking of HY-specific T lymphocytes into antigenic and nonantigenic tissue using in vivo models of T-cell recruitment. Up-regulated expression of H2 molecules presenting endogenous antigen in the peritoneal mesothelium and vessels led to the local recruitment of HY-specific T cells in male, but not female, mice. Intravital microscopy experiments analyzing EC–HY-specific T-cell interactions in the cremasteric vascular bed revealed that cognate recognition of the endothelium results in enhanced diapedesis of T cells into the tissue, while not affecting rolling and adhesion. Our results are consistent with the hypothesis that, under inflammatory conditions, antigen presentation by the endothelium contributes to the development and specificity of T-cell–mediated inflammation by favoring the selective migration of antigen-specific T cells. (Blood. 2004;103:3111-3116)
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