Inhibition of interleukin 4 receptor expression on human lymphoid cells by cyclosporin.
The effect of the immunosuppressant cyclosporin (CsA) on the expression of interleukin (IL) 4 membrane receptors on human peripheral blood mononuclear cells (PBMC) was investigated after cell activation by anti-CD3 antibody, IL 2 or IL 4. Previous studies with 125I-labeled IL 4 identified on resting lymphocytes a trimolecular complex consisting of a 65/70-kDa doublet and a 110-kDa protein with approximately 300 high-affinity binding sites (Kd 100 pM) and approximately 9000 low-affinity binding sites (Kd 30 nM). Upon cell activation by anti-CD3 antibody both low- and high-affinity binding sites increased about threefold concomitant with up-regulation of all the cross-linked proteins. CsA inhibited anti-CD3 antibody-induced up-regulation of IL 4 receptor (IL 4R)-associated proteins as well as the expression of high-affinity binding sites. However, up-regulation of IL 4R by its own ligand or IL 2 and the growth-promoting effect of IL 4 on activated, IL 4R+ T cells were CsA resistant. Since CsA inhibits the synthesis of IL 4, exogenous IL 4 was added to the cultures and it partially reversed the inhibitory effect of CsA on cell proliferation as well as on IL 4R expression. It is concluded that the inhibitory effect of CsA on IL 4R expression may contribute to the immunosuppressive effect of the drug.
Foxwell
B M
BM
Drug Safety Assessment, Sandoz Ltd., Basel, Switzerland.
Woerly
G
G
Ryffel
B
B
D000345:Affinity Labels; D015703:Antigens, CD / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D017252:CD3 Complex; D003432:Cross-Linking Reagents; D003524:Cyclosporins / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology; D015847:Interleukin-4 / Q000378:metabolism* / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects
D000345:Affinity Labels; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D003432:Cross-Linking Reagents; D003524:Cyclosporins; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4