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

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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 (Gαi 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.