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 vi...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2002-04, Vol.168 (7), p.3227-3234
Main Authors: Berg, Lutz-Peter, James, Martha J, Alvarez-Iglesias, Montserrat, Glennie, Sarah, Lechler, Robert I, Marelli-Berg, Federica M
Format: Article
Language:English
Subjects:
Antigens - pharmacology
CD4-Positive T-Lymphocytes - cytology
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - metabolism
Cell Communication - immunology
Cell Line, Transformed - immunology
Cell Movement - immunology
Cells, Cultured
Clone Cells
Endothelium, Vascular - cytology
Endothelium, Vascular - immunology
Humans
Immunologic Memory
Immunophenotyping
Integrin beta1 - metabolism
Integrin beta1 - physiology
Intercellular Adhesion Molecule-1 - metabolism
Intercellular Adhesion Molecule-1 - physiology
Lymphocyte Activation
NF-kappa B - biosynthesis
Signal Transduction - immunology
T-Lymphocyte Subsets - cytology
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - metabolism
Transcription Factor AP-1 - biosynthesis
Up-Regulation - immunology
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.168.7.3227