IL-4 down-regulates IL-2 receptor p75 by accelerating its endocytosis

We examined the effects of interleukin 4 (IL-4) on the expressionof IL-2 receptor p75 (IL-2R p75) or ß chain on varioushuman T cells. IL-4 promptly down-regulated surface IL-2 receptor(IL-2R) p75 In these cells. Although IL-2-lnduced IL-2R p75down-regulation was seen more quickly, IL-2 did not contributeto the process of the IL-4-induced decrease of IL-2R p75. Northernblotting revealed that IL-4 did not reduce the expression ofIL-2R p75 mRNA. Studies using Pronase E, which digests cellsurface IL-2R p75, or brefeldin A, which blocks Intracytoplasmicprotein transport from endoplasmicretculum to the Golgi apparatus,suggest that IL-4-lnduced IL-2R p75 down-reguation is controlledafter IL-2R p75 is expressed on the cell surface. We found thatIL-4 accelerated the endocytosis of IL-2R p75, which was monitoredby (¹²⁵)||M||k-ß3 monocional antibody that recognizesnon-IL-2-bindlng epitope on IL-2R p75. These findings demonstratethat IL-4 down-regulates IL-2R p75 mainly by accelerating Itsendocytosis.