Role of LFA-1/ICAM-1 in interleukin-2-stimulated lymphocyte proliferation.
Major adhesion routes between lymphoid cells involve the receptor/ligand pairs LFA-1/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 alpha or beta subunit of LFA-1 or to its ligand ICAM-1. Interestingly, rIL-2-induced proliferation was also inhibited by NKI-L16, and anti-1 alpha 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-1/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-1/ICAM-1 interaction. This suggests that LFA-1/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.
Vyth-Dreese
F A
FA
Division of Immunology, The Netherlands Cancer Institute, Amsterdam.
Dellemijn
T A
TA
Frijhoff
A
A
van Kooyk
Y
Y
Figdor
C G
CG
D000911:Antibodies, Monoclonal / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1