The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 313K)
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lee, I.-H.
Right arrow Articles by Ivashkiv, L. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, I.-H.
Right arrow Articles by Ivashkiv, L. B.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© The Rockefeller University Press, 0022-1007/1999/11/1263/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 9, November 1, 1999 1263-1274

Original Article

Inhibition of Interleukin 2 Signaling and Signal Transducer and Activator of Transcription (STAT)5 Activation during T Cell Receptor–mediated Feedback Inhibition of T Cell Expansion

In-Hong Leea, Wai Ping Lia, Katherine B. Hisertb, and Lionel B. Ivashkiva,c
a Department of Medicine, Hospital for Special Surgery, New York, New York 10021
b Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD-PhD Program, New York, New York 10021
c Graduate Program in Immunology, Weill Graduate School of Medical Sciences of Cornell University, New York, New York 10021

Correspondence to: Lionel B. Ivashkiv, Department of Medicine, Hospital for Special Surgery, 535 East 70th St., New York, NY 10021. Tel:212-606-1653 Fax:212-717-1192 E-mail:ivashkivl{at}hss.edu.

Limitation of clonal expansion of activated T cells is necessary for immune homeostasis, and is achieved by growth arrest and apoptosis. Growth arrest and apoptosis can occur passively secondary to cytokine withdrawal, or can be actively induced by religation of the T cell receptor (TCR) in previously activated proliferating T cells. TCR-induced apoptosis appears to require prior growth arrest, and is mediated by death receptors such as Fas. We tested whether TCR religation affects T cell responses to interleukin (IL)-2, a major T cell growth and survival factor. TCR ligation in activated primary human T cells blocked IL-2 induction of signal transducer and activator of transcription (STAT)5 DNA binding, phosphorylation of STAT5, Janus kinase (Jak)1, Jak3, and Akt, and kinase activity of Jak1 and Jak3. Inhibition was mediated by the mitogen-activated protein kinase kinase (MEK)–extracellular stimulus–regulated kinase (ERK) signaling pathway, similar to the mechanism of inhibition of IL-6 signaling we have described previously. TCR ligation blocked IL-2 activation of genes and cell cycle regulatory proteins, and suppressed cell proliferation and expansion. These results identify TCR-induced inhibition of IL-2 signaling as a novel mechanism that underlies antigen-mediated feedback limitation of T cell expansion, and suggest that modulation of cytokine activity by antigen receptor signals plays an important role in the regulation of lymphocyte function.

Key Words: cytokines, signal transduction, inhibition, mitogen-activated protein kinases, gene activation


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS