RANTES stimulation of T lymphocyte adhesion and activation: role for LFA-1 and ICAM-3

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 beta 1 and beta 2 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 (G alpha 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 alpha 4 or beta 1 integrins. Intercellular adhesion molecule-3 (ICAM-3) and possibly ICAM-1 participate as LFA-1 ligands. Additionally, RANTES phosphorylated the beta 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.