Regulatory effect of interleukin-4 (IL-4) on the expression and function of lymphocyte adhesion receptors involved in IL-2-induced cell aggregation.
Human recombinant interleukin-4 (rIL-4) was studied for its capacity to inhibit rIL-2-induced lymphoid cell aggregation. In contrast to rIL-2, rIL-4 was unable to induce cluster formation by itself. However, when added simultaneously with rIL-2 to cultures of freshly isolated peripheral blood lymphocytes (PBL), rIL-4 inhibited cell aggregation in a dose-dependent way. In contrast, PBL, preactivated by a 4-day culture in the presence of 500 U/ml rIL-2, were not inhibited in their adhesive capacity by rIL-4. Inhibition of cell aggregation was most prominent at 24 hr and virtually lost after 72 hr of culture. Phenotypical analysis revealed that rIL-4, with similar kinetics, decreased the rIL-2-mediated up-regulation of the CD2, CD54 and CD49e adhesion molecules. In addition, it was observed that up-regulation of the activation epitope on CD11a recognized by the mAb NKI-L16, was prevented. During 24hr of culture rIL-4 itself did not alter the expression of these antigens. Blocking experiments with mAb directed against adhesion structures did not reveal a direct role for CD49e, but obviously demonstrated involvement of CD11a/CD18-CD54 and CD2-CD58 interactions in the rIL-2-induced adhesion. Therefore, rIL-4 appears to inhibit the early phase of rIL-2-induced aggregation by preventing the up-regulation of CD54 and CD2 antigens and by inhibiting the generation of the activated state of the CD11a/CD18 receptor.
Vyth-Dreese
F A
FA
Division of Immunology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Huis, Amsterdam.
Van Kooyk
Y
Y
Dellemijn
T A
TA
Melief
C J
CJ
Figdor
C G
CG
D015815:Cell Adhesion Molecules / Q000032:analysis; D002449:Cell Aggregation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology* / Q000494:pharmacology; D007700:Kinetics; D016028:Receptors, Leukocyte-Adhesion / Q000032:analysis*; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D007376:Interleukin-2; D016028:Receptors, Leukocyte-Adhesion; D011994:Recombinant Proteins; D015847:Interleukin-4