Expression of the interleukin-2 receptor on human fibroblasts and its biological significance

Abstract

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 [125I]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 [125I]IL-2 labelling shows the presence of both high affinity (150 sites with a Kd of 147 pM) and low affinity (1100 sites with a Kd 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Functional IL-2 Receptor β (CD122) and γ (CD132) Chains Are Expressed by Fibroblast-Like Synoviocytes: Activation by IL-2 Stimulates Monocyte Chemoattractant Protein-1 Production

“…Analysis of the cell surface expression of CD122 demonstrated that the DF displayed fewer Ag binding sites per cell than FLS. However, this number of sites per cell was in accordance with the previously quantified number of low affinity sites recorded for embryonic fibroblasts (23). The number of receptors expressed may well influence or provide a threshold for the response following IL-2 stimulation.…”

“…The lack of expression of CD25 by both FLS and DF confirmed the previous findings for DF (23). However, this is the first time that the important observation has been made that CD122 is constitutively expressed by FLS and adult DF.…”

“…However, cells other than T cells, such as monocytes, express functional CD122 and CD132 and have the ability to signal following ligation of the intermediate affinity receptor consisting of the heterodimer formed by CD122 and CD132. Plaisance et al (23) and Gruss et al (24) have shown that CD25 and CD122 are expressed on human embryonic fibroblasts, with loss of the CD25 in adult cells. Keratinocytes also express the CD122, but with variable expression of CD132 (25).…”

Interleukin-2 expression in human carcinoma cell lines and its role in cell cycle progression

“…The IL-2R appears to be expressed not only on hematopoietic cells but also on a wide variety of non-hematopoietic cells, including normal and malignant cells of the epithelial origin (Saneto et al, 1986;Weidmann et al, 1992;Plaisance et al, 1992Plaisance et al, , 1993Artz et al, 1992;Alileche et al, 1993;Ciacci et al, 1993;Yasumura et al, 1994;Lin et al, 1995;McMillan et al, 1995). Functions of the IL-2R chains in nonhematopoietic cells are not fully understood.…”

Endogenous IL-15 Sustains Recruitment of IL-2Rβ and Common γ and IL-2-Mediated Chemokine Production in Normal and Inflamed Human Gingival Fibroblasts

“…Activation through IL-2R␤ and ␥ c is directly associated with phosphorylation of Jak1 and Jak3, resulting in STAT3 and STAT5 phosphorylation, respectively (10). It has been shown that human monocytes also bear functional IL-2R␤ and ␥ c (11), human fibroblasts from adult bone marrow, embryonic skin, and lung express IL-2R␣ and IL-2R␤ (12)(13)(14), and fibroblast-like synoviocytes express functional IL-2R␤ and ␥ c (15). In addition, we have recently shown that normal HGF express functional IL-2R␤ and ␥ c and that IL-2 stimulation induced production of MCP-1 and expression of ICAM-1 by HGF, resulting in the augmentation of ICAM-1-mediated neutrophil adhesion, and that the IL-2-induced MCP-1 production was significantly inhibited by pretreatment with anti-IL-15 neutralizing mAb (16).…”