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Costimulation by interleukin-1 of multiple activation responses in a developmentally restricted subset of immature thymocytes

Rothenberg, Ellen V. and Diamond, Rochelle A. (1994) Costimulation by interleukin-1 of multiple activation responses in a developmentally restricted subset of immature thymocytes. European Journal of Immunology, 24 (1). pp. 24-33. ISSN 0014-2980. https://resolver.caltech.edu/CaltechAUTHORS:20170206-143349258

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Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1002/eji.1830240105DOIArticle
http://onlinelibrary.wiley.com/doi/10.1002/eji.1830240105/abstractPublisherArticle
ORCID:
AuthorORCID
Rothenberg, Ellen V.0000-0002-3901-347X
Additional Information:© 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.
Funders:
Funding AgencyGrant Number
NIHAI19752
Lucille P. Markey Charitable TrustUNSPECIFIED
Caltech Beckman InstituteUNSPECIFIED
Subject Keywords:CD25; Interleukin 2; Cell cycle; Signaling; cAMP
Issue or Number:1
Record Number:CaltechAUTHORS:20170206-143349258
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170206-143349258
Official Citation:Rothenberg, E. V. and Diamond, R. A. (1994), Costimulation by interleukin-1 of multiple activation responses in a developmentally restricted subset of immature thymocytes. Eur. J. Immunol., 24: 24–33
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74095
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:07 Feb 2017 00:11
Last Modified:03 Oct 2019 16:34

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