Role of LFA‐1/ICAM‐1 in interleukin‐2‐stimulated lymphocyte proliferation

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Abstract
Major adhesion routes between lymphoid cells involve the receptor/ligand pairs LFA‐l/ICAM‐1 and CD2/LFA‐3, in addition to VLA or CD44 molecules. In this study we evaluated the role of these adhesion receptors in the proliferative response of lymphoid cells to interleukin‐2 (IL‐2). Blocking studies were performed with a panel of monoclonal antibodies (mAb) directed against these adhesion molecules. Selective inhibition of recombinant (r)IL‐2‐induced cell proliferation was observed with mAb directed against the a or /3 subunit of LFA‐1 or to its ligand ICAM‐1. Interestingly, rIL‐2‐induced proliferation was also inhibited by NKI‐L16, an anti‐la antibody known to enhance cell‐cell interaction. Resting lymphocytes were preferentially susceptible to the inhibition, particularly in an early phase of culture and when stimulated with a relatively low dose of rIL‐2. By using mAb that specifically could block distinct rIL‐2 activation pathways, LFA‐l/ICAM‐1 interaction was found to be required for p55 IL‐2 receptor (IL‐2R)‐mediated interaction of rIL‐2 with its high‐affinity receptor, but not for p75 IL‐2R‐mediated responses. Furthermore, it was shown that the rIL‐2 response of T lymphocytes, but not of natural killer cells, was dependent on LFA‐l/ICAM‐1 interaction. This suggests that LFA‐l/ICAM‐1 interaction is required for an optimal rIL‐2 response of cells capable of IL‐2 secretion. Our data provide evidence for the hypothesis that adhesion receptor‐directed release of IL‐2 may result in a locally high concentration of IL‐2 that triggers high‐affinity IL‐2R signaling and up‐regulates p55 IL‐2R to enhance cytokine responsiveness.