Interleukin-3-induced downregulation of the expression of interleukin-2 receptor beta chain in human T cells.
We examined the effect of interleukin-3 (IL-3) on human CD4+ cloned T cells, P607 and 1C2. By flow cytometric analysis, we found that IL-3 downregulated the surface expression of IL-2 receptor (R) beta chain in a dose-dependent manner but had little effect on that of IL-2R alpha chain. A simultaneous 125I-labeled IL-2 binding assay showed a decrease in the number of high-affinity, but not of low-affinity, IL-2Rs by IL-3. The downregulation of the IL-2R beta chain began 3 hours after culture initiation, increased further thereafter, and was completely inhibited by anti-IL-3 antibodies. Expression of mRNA for either alpha or beta chain was not reduced by IL-3, and this suggests that the reduction of surface beta chain expression was not caused by the reduction of beta chain mRNA. IL-3-accelerating internalization of IL-2R beta chain appeared to be one of the mechanisms for IL-3-induced downregulation of surface IL-2R beta chain expression. IL-3 alone increased the proliferation of T-cell clones but decreased the existing increment of their proliferation by IL-2. Accordingly, IL-3 may be one of the factors acting as a liaison between the hematopoietic and immune systems.
Onishi
R
R
First Division of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Ishikawa
T
T
Kodaka
T
T
Okuma
M
M
Uchiyama
T
T
D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D015536:Down-Regulation; D004705:Endocytosis; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000502:physiology; D007377:Interleukin-3 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
D007376:Interleukin-2; D007377:Interleukin-3; D015375:Receptors, Interleukin-2