title: Down-regulation of high affinity interleukin 2 receptors in a human tumor T cell line. Interleukin 2 increases the rate of surface receptor decay.
abstract: We have described a human tumor T cell line, IARC 301, which constitutively expresses high affinity interleukin 2 (IL2) receptors, and showed that after binding to its receptors, IL2 is endocytosed and degraded. Here we present evidence that IL2 down-regulates its own high affinity receptors. Within 1 h, IL2 induces a 60% decrease in surface receptor expression. In order to maintain this down-regulation, IL2 concentration must be high enough for the receptors to be saturated throughout the incubation. The effect of IL2 on the kinetics of receptor internalization was investigated with two approaches. First, the initial rate of IL2 internalization was measured, and no difference could be detected whether the receptors were saturated with IL2 or only partially occupied. Second, the initial rate of surface receptor decay was followed and found to be significantly decreased in the presence of IL2. Although the half-life of IL2 receptors is very short in the absence of IL2, t 1/2 approximately 65 min, suggesting that these receptors are constantly endocytosed, it can still be reduced to t 1/2 approximately 25 min when the receptors are saturated with ligand. This suggests that occupied receptors are internalized faster than and independently from free receptors. The difference in internalization rates can explain the observed receptor down-regulation.
mesh_terms: D000465:Algorithms; D002460:Cell Line; D006207:Half-Life; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D008223:Lymphoma / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes
chemical_list: D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2