The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 274K)
Right arrow PPT slides of all figures
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 Saoulli, K.
Right arrow Articles by Watts, T. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Saoulli, K.
Right arrow Articles by Watts, T. H.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*Protein
*UniGene
*Substance via MeSH
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/1998/6/1849/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 11, June 1, 1998 1849-1862

Articles

CD28-independent, TRAF2-dependent Costimulation of Resting T Cells by 4-1BB Ligand

Katina Saoulli*, Soo Young Lee||, Jennifer L. Cannons*, Wen Chen Yeh{ddagger}, Angela Santana{ddagger}, Marni D. Goldstein*, Naveen Bangia*, Mark A. DeBenedette*, Tak W. Mak*,{ddagger}, Yongwon Choi§,||, and Tania H. Watts*

From the * Department of Immunology, the {ddagger} Department of Medical Biophysics, and Amgen Institute, University of Toronto, Toronto, Ontario M5S 1A8, Canada; and the § Howard Hughes Medical Institute and || The Rockefeller University, New York 10021

4-1BB ligand (4-1BBL) is a member of the tumor necrosis factor (TNF) family expressed on activated antigen-presenting cells. Its receptor, 4-1BB, is a member of the TNF receptor family expressed on activated CD4 and CD8 T cells. We have produced a soluble form of 4-1BBL using the baculovirus expression system. When coimmobilized on plastic with anti-CD3, soluble 4-1BBL induces interleukin (IL)-2 production by resting CD28+ or CD28– T cells, indicating that 4-1BBL can function independently of other cell surface molecules, including CD28, in costimulation of resting T cell activation. At low concentrations of anti-CD3, 4-1BBL is inferior to anti-CD28 in T cell activation. However, when 4-1BB ligand is provided together with strong TCR signals, then 4-1BBL and anti-CD28 are equally potent in stimulation of IL-2 production by resting T cells. We find that TNF receptor–associated factor (TRAF)1 or TRAF2 associate with a glutathione S-transferase–4-1BB cytoplasmic domain fusion protein in vitro. In T cells, we find that association of TRAF1 and TRAF2 with 4-1BB requires 4-1BB cross-linking. In support of a functional role for TRAF2 in 4-1BB signaling, we find that resting T cells isolated from TRAF2-deficient mice or from mice expressing a dominant negative form of TRAF2 fail to augment IL-2 production in response to soluble 4-1BBL. Thus 4-1BB, via the TRAF2 molecule, can provide CD28-independent costimulatory signals to resting T cells.

Key Words: T cells • costimulation • 4-1BB • TRAF2 • signaling

Address correspondence to Dr. Tania H. Watts, Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada. Phone: 416-978-4551; Fax: 416-978-1938; E-mail: tania.watts{at}utoronto.ca

Abbreviations used: 4-1BBL, 4-1BB ligand; AP, alkaline phosphatase; CT, cytoplasmic tail; DN, dominant negative; GST, glutathione S-transferase; HA, hemagglutinin; ICAM-1, intercellular adhesion molecule 1; JNK, c-Jun NH2-terminal kinase; NF-{kappa}B, nuclear factor–{kappa}B; RT, reverse transcriptase; s4-1BBL, soluble form of 4-1BBL; TRAF, TNF receptor–associated factor.


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 Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



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