Chemokines fail to up-regulate β1 integrin-dependent adhesion in human Th2 T lymphocytes

Barbara Clissi, Daniele D'Ambrosio, Jens Geginat, Lucia Colantonio, Alexander Morrot, Norman W. Freshney, Julian Downward, Francesco Sinigaglia, Ruggero Pardi

Research output: Contribution to journalArticlepeer-review

Abstract

Th1 and Th2 cells are functionally distinct subsets of CD4+ T lymphocytes whose tissue-specific homing to sites of inflammation is regulated in part by the differential expression of P- and E-selectin ligands and selected chemokine receptors. Hero we investigated the expression and function of β1 integrins in Th1 and Th2 cells polarized in vitro. Th1 lymphocytes adhere transiently to the extracellular matrix ligands laminin 1 and fibronectin in response to chemokines such as RANTES and stromal cell- derived factor-1, and this process is paralleled by the activation of the Rac1 GTPase and by a rapid burst of actin polymerization. Selective inhibitors of phosphoinositide-3 kinase prevent efficiently all of the above processes, whereas the protein kinase C inhibitor bisindolylmaleimide prevents chemokine-induced adhesion without affecting Rac1 activation and actin polymerization. Notably, chemokine-induced adhesion to β1 integrin ligands is markedly reduced in Th2 cells. Such a defect cannot be explained by a reduced sensitivity to chemokine stimulation in this T cell subset, nor by a defective activation of the signaling cascade involving phosphoinositide-3 kinase, Rac1, and actin turnover, as all these processes are activated at comparable levels by chemokines in the two subsets. We propose that reduced β1 integrin-mediated adhesion in Th2 cells may restrain their ability to invade and/or reside in sites of chronic inflammation, which are characterized by thickening of basement membranes and extensive fibrosis, requiring efficient interaction with organized extracellular matrices.

Original languageEnglish
Pages (from-to)3292-3300
Number of pages9
JournalJournal of Immunology
Volume164
Issue number6
Publication statusPublished - Mar 15 2000

ASJC Scopus subject areas

  • Immunology

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