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RANTES stimulation of T lymphocyte adhesion and activation: role for LFA‐1 and ICAM‐3
Author(s) -
Szabo Margit C.,
Butcher Eugene C.,
McIntyre Bradley W.,
Schall Thomas J.,
Bacon Kevin B.
Publication year - 1997
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830270504
Subject(s) - lymphocyte function associated antigen 1 , cd28 , microbiology and biotechnology , t cell , biology , chemokine , integrin , cell adhesion , cell adhesion molecule , intercellular adhesion molecule , chemotaxis , chemokine receptor , intercellular adhesion molecule 1 , immunology , receptor , cell , immune system , biochemistry
Abstract The chemokine RANTES is a potent chemoattractant and activator of T lymphocytes. Mechanisms underlying the RANTES‐induced activation of T lymphocytes leading to adhesion and migration have not been fully analyzed. We investigate here the function of RANTES in the regulation of T cell adhesion, specifically the induction of homotypic aggregation. RANTES induced the expression of many important cell surface adhesion and activation receptors in a normal human T cell clone and peripheral blood T lymphocytes, including members of the β1 and β2 integrin family, CD44, CD50, and CD28. Up‐regulation of these markers correlated with RANTES‐stimulated homotypic adhesion of T cells. This homotypic aggregation event was RANTES dose‐dependent, prolonged, and pertussis toxin‐independent, but herbimycin A‐sensitive, suggesting that it involves signaling through alternative (Gα i protein‐independent) pathways. Using specific monoclonal antibodies, the homotypic aggregation event was shown to be lymphocyte function‐associated antigen‐1 (LFA‐1)‐dependent, with no observable interaction through α4 or β1 integrins. Intercellular adhesion molecule‐3 (ICAM‐3) and possibly ICAM‐1 participate as LFA‐1 ligands. Additionally, RANTES phosphorylated the β chain of LFA‐1 1–2 min following stimulation. These results imply a specific role for the chemokine RANTES in T cell activation and intercellular adhesion.