PI3Kδ promotes CD4 + T‐cell interactions with antigen‐presenting cells by increasing LFA‐1 binding to ICAM‐1

Activation of T lymphocytes by peptide/major histocompatibility complex on antigen‐presenting cells (APCs) involves dynamic contacts between the two cells, during which T cells undergo marked morphological changes. These interactions are facilitated by integrins. Activation of the T cells increases the binding of the integrin lymphocyte function‐associated antigen 1 (LFA‐1) expressed by T cells to intercellular adhesion molecule (ICAM)‐1 and ICAM‐2 expressed by APCs. The signalling pathways that control integrin affinities are incompletely defined. The phosphoinositide 3‐kinases (PI3Ks) generate second‐messenger signalling molecules that control cell growth, proliferation, differentiation and trafficking. Here we show that in T cells, PI3Kδ attenuates the activation of Rac1, but sustains the activation of Rap1. Consequently, PI3Kδ increases LFA‐1‐dependent adhesion to form stable conjugates with APCs. Increased Rap1 activity and LFA‐1 adhesion were only in part mediated by the downstream kinase Akt, suggesting the involvement of additional phosphatidylinositol(3,4,5)P 3 ‐binding proteins. These results establish a link between PI3K activity, cytoskeletal changes and integrin binding and help explain the impaired T‐cell‐dependent immune responses in PI3Kδ‐deficient mice.