Functional consequences of noncognate interactions between CD4+ memory T lymphocytes and the endothelium.
The recruitment of Ag-specific T cells to sites of inflammation is a crucial step in immune surveillance. Although the molecular interactions controlling T cell extravasation are relatively well characterized, the effects of these events on T cell function are still poorly understood. Using an in vitro model of transendothelial migration of human CD4(+) memory T cells, we have investigated the molecular and functional changes induced in T cells that come into contact with the endothelium. First, we show that transendothelial migration is precluded by signals that lead to T cell division. In addition, activation of the transcription factor AP-1, without induction of NF-kappaB, is observed in T cells after noncognate interactions with endothelial cells (EC), a pattern of transcriptional regulation different from that observed in dividing T cells. Up-regulation of certain adhesion (CD11a, CD49d), activation (CD69), and costimulatory (CD86) receptors accompany these transcriptional events. Most importantly, recently migrated T cells display a faster rate of migration when reseeded onto an EC monolayer. Finally, T cells become hyperresponsive to antigenic challenge after noncognate interactions with the endothelium. These effects appear not to be due to the selection of preactivated T lymphocytes, because they occur also in clonal T cell populations and appear to be mediated by alpha(L)beta(2) integrin-CD54 interactions. We conclude that CD4(+) memory T cell extravasation is accompanied by phenotypic and functional changes induced by the interactions with the EC, which favor tissue infiltration by T cells and their further activation once they reach the antigenic site.
Berg
Lutz-Peter
LP
Department of Immunology and Histopathology, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom.
James
Martha J
MJ
Alvarez-Iglesias
Montserrat
M
Glennie
Sarah
S
Lechler
Robert I
RI
Marelli-Berg
Federica M
FM
D000941:Antigens / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D002461:Cell Line, Transformed / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells; D004730:Endothelium, Vascular / Q000166:cytology* / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D019012:Integrin beta1 / Q000378:metabolism / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism / Q000502:physiology; D008213:Lymphocyte Activation; D016328:NF-kappa B / Q000096:biosynthesis; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000096:biosynthesis; D015854:Up-Regulation / Q000276:immunology
D000941:Antigens; D019012:Integrin beta1; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D018799:Intercellular Adhesion Molecule-1