High-affinity and intermediate-affinity forms of the human interleukin 2 receptor, expressed in an interleukin 9-dependent murine T cell line, deliver proliferative signals via differences in their transduction pathways.
Although several reports have claimed that the p70 IL-2R per se transduces a growth signal in lymphoid and non-lymphoid systems, there is no convincing evidence for this in lymphoid T cell lines. In order to investigate the mechanism of IL-2R-dependent signal transduction pathways via the p70 IL-2R in lymphoid T cells, we have established two IL-9-dependent murine (TS1) cell lines stably expressing the human p70 IL-2R subunit or the human p55-p70 IL-2R complex. Whereas the parental T cell line, TS1, proliferated in response to IL-9 or IL-4 but not IL-2, cell lines stably expressing human p70 IL-2R or p55-p70 IL-2R complex proliferated in response to IL-2. This implies that the murine T cell, TS1, contains all the intracellular components necessary for directing IL-2 signalling. In human p55-p70 IL-2R-transfected cells, the expression of a functional murine p55 IL-2R seemed to be induced and regulated by IL-2. In human p70 IL-2R-transfected cells, in the presence of IL-2 an interaction requiring only intermediate-affinity was sufficient for transduction of a proliferative signal. In addition human p70 IL-2R per se, is biologically functional via a transduction pathway not requiring induction of murine p55 IL-2R and consecutive high-affinity complex reconstitution. Thus, although both transfected cell lines can transduce a proliferative signal in the presence of IL-2, a difference in their transduction pathway is probably involved for the induction of p55 IL-2R.
Pitton
C
C
Unité d'Immunogénétique Cellulaire, Institut Pasteur, Paris, France.
Rebollo
A
A
Van Snick
J
J
Thèze
J
J
Garcia
A
A
D000818:Animals; D000911:Antibodies, Monoclonal; D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D016906:Interleukin-9 / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D014162:Transfection
D000911:Antibodies, Monoclonal; D018076:DNA, Complementary; D016906:Interleukin-9; D015375:Receptors, Interleukin-2