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 recept or (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. CD^(25+) expression is amplified by IL-1 through a mechanism highly sensitive to changes in Ca^(2+) 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 CD^(25+) 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 CD^(25+) 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.
© 1994 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Manuscript Accepted: 21 September 1993; Manuscript Revised: 14 September 1993; Manuscript Received: 5 July 1993. Funded by: USPHS. Grant Number: (AI 19752); The Lucille Markey Charitable Trust Program in Developmental Biology at Caltech; The Flow Cytometry Facility was supported by funds from the Markey Program and from the Beckman Institute at Caltech.