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IL-2 gene inducibility in T cells before T cell receptor expression. Changes in signaling pathways and gene expression requirements during intrathymic maturation

Rothenberg, Ellen V. and Diamond, Rochelle A. and Pepper, Karen A. and Yang, Julia A. (1990) IL-2 gene inducibility in T cells before T cell receptor expression. Changes in signaling pathways and gene expression requirements during intrathymic maturation. Journal of Immunology, 144 (5). pp. 1614-1624. ISSN 0022-1767. https://resolver.caltech.edu/CaltechAUTHORS:20170207-105303837

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Abstract

The ability to express the growth hormone IL-2 upon stimulation gives T lymphocytes one of their major effector functions in the immune system. IL-2 is apparently synthesized only by T cells, and only by a subset of T cells which constitutes a "helper" class. It remains unknown how and when the IL-2-producing lineage becomes distinct from other functional effector lineages. We have therefore examined immature T cell precursors to determine when IL-2 inducibility is acquired in relation to other maturation events, such as expression of an Ag-binding TCR, which is suspected to play an influential role in the determination of subclass commitment. In mature T cells, IL-2 is inducible via agonists of the phosphoinositide pathway, a network of signaling mediators shared by a wide variety of metazoan cell types. The universality of this activation pathway makes it seem less likely, a priori, to be a target of developmental change than the intrinsic susceptibility to induction of the IL-2 locus. However, our results presented here refute this expectation. In this report, we show that both TCR+ cells and pre-T cells too immature to express TCR can be induced to express IL-2 at high levels. The induction requirements for IL-2 expression, however, are different in TCR^- and TCR^+ cells. Even by using Ca^(2+) ionophore and phorbol ester to bypass the requirement for the TCR in cell activation, the TCR^- cells also require the presence of the polypeptide hormone IL-1. By contrast, TCR^+ mature cells not only can express IL-2 without IL-1, but also show no response to IL-1 when Ca^(2+) ionophore and phorbol ester are present. IL-1-dependent IL-2 producers appear in the thymus of repopulating radiation chimeras before "mature" (TCR^+) T cells, whereas IL-1-independent IL-2 production is found only afterward. Thus, IL-2 inducibility per se apparently precedes TCR expression and all TCR-associated fate determination events. However, developmental alteration of signal transduction pathways may play a vital regulatory role in the later allocation of particular functional responses to appropriate lineages of T cells.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://www.jimmunol.org/content/144/5/1614PublisherArticle
ORCID:
AuthorORCID
Rothenberg, Ellen V.0000-0002-3901-347X
Additional Information:© 1990 The American Association of Immunologists. Received for publication August 29. 1989. Accepted for publication November 22, 1989. This work was supported by Grants AI19752 and CA39605 from the U.S. Public Health Service (USPHS), and by a Biomedical Research Support Grant (USPHS) to the Caltech Division of Biology. The flow cytometry facility was supported by Grant CA32911 from the National Cancer Institute and by an Instrumentation Support Grant from the Markey Developmental Biology Program at Caltech. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement In accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Funders:
Funding AgencyGrant Number
NIHAI19752
NIHCA39605
NIHCA32911
Lucille P. Markey Charitable TrustUNSPECIFIED
Issue or Number:5
Record Number:CaltechAUTHORS:20170207-105303837
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170207-105303837
Official Citation:IL-2 gene inducibility in T cells before T cell receptor expression. Changes in signaling pathways and gene expression requirements during intrathymic maturation. E V Rothenberg, R A Diamond, K A Pepper, J A Yang The Journal of Immunology March 1, 1990, 144 (5) 1614-1624
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74133
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:07 Feb 2017 19:51
Last Modified:03 Oct 2019 16:35

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