EXPRESSION OF THE INTERLEUKIN-2 RECEPTOR ON HUMAN FIBROBLASTS AND ITS BIOLOGICAL SIGNIFICANCE

In this study, we have investigated the expression of the alpha and beta-chains of the IL-2 receptor (IL-2R-alpha, IL-2R-beta) both at the membrane and at transcriptional levels during the lifespan of human embryonic fibroblasts. Here we show that the mAbs IOT14 and MIK-beta-1 directed against the IL-2 binding sites of the IL-2R-alpha and IL-2R-beta respectively, stain human embryonic fibroblasts early in their life span. Data from [I-125]rIL2 cross-linking experiments show the simultaneous expression of two IL-2 binding peptides of 70 and 55 kDa respectively on embryonic young fibroblasts as on lymphoid activated cells. The p55 and the p70 IL-2 binding peptides are shown to be specific for the IL-2R-alpha and to the IL-2R-beta by the finding that these bands are abolished by excess amounts of cold IL-2 and mAbs directed against the IL-2 binding sites of the alpha and beta-chains. Scatchard analysis after [I-125]IL-2 labelling shows the presence of both high affinity (150 sites with a K(d) of 147 pM) and low affinity (1100 sites with a K(d) of 4 nM) IL-2 binding sites. Northern blot and dot blot analysis show the presence of specific transcripts for the IL-2R-alpha and IL-2R-beta genes in early passaged fibroblasts. By contrast, in senescent cultures, only the IL-2R-beta transcript were detected. Finally, IL-2 at low concentrations (36 pM) down modulates the level of the intercellular adhesion molecule ICAM-1 in young but not in senescent cultures. Changes in the expression of the IL-2R-alpha during aging process probably affect the regulation of the ICAM-1 dependent fibroblastic functions.