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Influence of activating stimulus on functional phenotype: Interleukin 2 mRNA accumulation differentially induced by ionophore and receptor ligands in subsets of murine T cells

McGuire, Kathleen L. and Yang, Julia A. and Rothenberg, Ellen V. (1988) Influence of activating stimulus on functional phenotype: Interleukin 2 mRNA accumulation differentially induced by ionophore and receptor ligands in subsets of murine T cells. Proceedings of the National Academy of Sciences of the United States of America, 85 (17). pp. 6503-6507. ISSN 0027-8424.

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We have investigated the linkage between CD4/CD8 phenotype and programing for specific responses in primary T-cell populations. In situ hybridization has been used to determine the frequency of cells competent to express the interleukin 2 (IL-2) gene after short-term stimulation with various polyclonal activators. The effects of the T-cell receptor ligands Con A and anti-CD3 monoclonal antibody were compared with those of a calcium ionophore that bypasses membrane receptors altogether. Induction with a calcium ionophore and phorbol ester revealed that potential IL-2 producers not only constitute >85% of the cells with a CD4+ "helper/inducer" phenotype but also constitute over half of the cells with a CD8+ "killer/suppressor" phenotype. There is no defect in the ability of these CD8+ cells to accumulate IL-2 transcripts under these conditions. By contrast, in response to phorbol ester and either Con A or anti-CD3, the CD8+ cells show an abortive IL-2 production response with rapid disappearance of IL-2 mRNA. This results in substantially lower yields of IL-2 per cell than is made by CD4+ cells in response to the same stimuli. The extent to which these populations appear to have diverged in function thus depends on the stimulus used to trigger the response. The results suggest that differences in signal transduction or posttranscriptional regulatory mechanisms, rather than effector gene inducibility per se, may initially underlie the commitment of CD4+ and CD8+ cells to distinct functional roles.

Item Type:Article
Additional Information:© 1988 by the National Academy of Sciences. Communicated by Ray D. Owen, May 31, 1988 (received for review November 23, 1987). We are grateful to Rochelle Diamond and Patrick Koen, who performed the flow cytometry; to Sharon Kochik for excellent technical assistance; to Thomas Novak for IL-2 gene constructs and useful suggestions on making probes; and to Drs. David Anderson, Paul Boyer, Eric Davidson, Norman Davidson, and Paul Sternberg for valuable comments and thoughtful criticism of the manuscript. We also thank Drs. Robert Hyman and Jeffrey Bluestone for their invaluable gifts of antibodies. K.L.M. was the recipient of National Cancer Institute Postdoctoral Fellowship CA-07876. J.A.Y. was supported by a National Institutes of Health training grant. This work was funded by Grants A119752 and CA39605 from the U.S. Public Health Service to E.V.R. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Subject Keywords:in situ hybridization; RNA probe protection; CD4, CD8; anti-CD3
Record Number:CaltechAUTHORS:MCGpnas88
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:9131
Deposited By: Tony Diaz
Deposited On:31 Oct 2007
Last Modified:14 Nov 2014 19:20

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