Costimulation by interleukin-1 of multiple activation responses in a developmentally restricted subset of immature thymocytes.
An intriguing feature of thymocyte differentiation is that the competence to express both interleukin-(IL)2 and CD25 is acquired even prior to T cell receptor (TcR) expression. When T cell receptor-independent stimuli are used, immature cells can express IL-2 at levels comparable to mature cells, but unlike the mature cells, immature cells require IL-1 as a costimulus. Here we present evidence that IL-1 affects a variety of responses by members of the CD25+ subset of immature thymocytes. Cells in this population are IL-1 dependent not only for induction of IL-2 expression, but also for high-level maintenance of CD25 expression. CD25 expression is amplified by IL-1 through a mechanism highly sensitive to changes in Ca2+ ionophore concentration. The effects of IL-1 on CD25 maintenance are not mediated by IL-2, because of the divergent effects of cAMP on IL-2 and CD25 expression. IL-1 costimulation also increases RNA accumulation in the cell cycle, and this effect too seems to be separable from the effects on IL-2 and CD25 expression. All these effects of IL-1 are developmentally stage-specific, manifest in the CD25+ subset of immature thymocytes but not in later-stage thymocytes or splenic T cells. Multiparameter cell sorting experiments that dissect the transitional stages between immature and TcR+ thymocytes imply that all immature cells pass through an IL-1 responsive state. Responsiveness to IL-1 costimulation is then lost by these cells, apparently irreversibly, at a stage just prior to detectable cell-surface TcR expression. These results indicate that IL-1 responsiveness is a defining characteristic of the activation physiology of cells in a particularly important developmental stage.
Division of Biology, California Institute of Technology, Pasadena 91125.
E V
EV
Rothenberg
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RA
Diamond
D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D002453:Cell Cycle / Q000502:physiology; D002478:Cells, Cultured; D005434:Flow Cytometry; D007375:Interleukin-1 / Q000502:physiology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology*
D000943:Antigens, Differentiation; D007375:Interleukin-1; D007376:Interleukin-2; D015375:Receptors, Interleukin-2