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, 134K)
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 Punt, J. A.
Right arrow Articles by Singer, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Punt, J. A.
Right arrow Articles by Singer, A.
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, 0022-1007/1997/12/1911/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 11, December 1, 1997 1911-1922

Articles

T Cell Receptor (TCR)-induced Death of Immature CD4+CD8+ Thymocytes by Two Distinct Mechanisms Differing in Their Requirement for CD28 Costimulation: Implications for Negative Selection in the Thymus

Jennifer A. Punt*, Wendy Havran§, Ryo Abe{ddagger}, Apurva Sarin*, and Alfred Singer*

From the * Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892; {ddagger} Immune Cell Biology Department, Naval Medical Research Institute, Bethesda, Maryland 20889-5607; and § Department of Immunology, Scripps Research Institute, La Jolla, California 92037

Negative selection is the process by which the developing lymphocyte receptor repertoire rids itself of autoreactive specificities. One mechanism of negative selection in developing T cells is the induction of apoptosis in immature CD4+CD8+ (DP) thymocytes, referred to as clonal deletion. Clonal deletion is necessarily T cell receptor (TCR) specific, but TCR signals alone are not lethal to purified DP thymocytes. Here, we identify two distinct mechanisms by which TCR-specific death of DP thymocytes can be induced. One mechanism requires simultaneous TCR and costimulatory signals initiated by CD28. The other mechanism is initiated by TCR signals in the absence of simultaneous costimulatory signals and is mediated by subsequent interaction with antigen-presenting cells. We propose that these mechanisms represent two distinct clonal deletion strategies that are differentially implemented during development depending on whether immature thymocytes encounter antigen in the thymic cortex or thymic medulla.

Address correspondence to Alfred Singer, Experimental Immunology Branch, NCI/NIH, Bldg 10, Rm 4B-17, Bethesda, MD 20892. Phone: 301-496-5461; Fax: 301-496-0887; E-mail: singera{at}nih.gov Dr. Punt's current address is Haverford College, Haverford, Pennsylvania, 19041. Dr. Abe's current address is Research Institute for Biological Sciences, Science University of Tokyo, 2669 Yamazaki, Noda City, Chiba 278, Japan.

This report was supported in part by National Medical Research and Development Command EQ.0095.003.1412. The views expressed in the article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the US Government.

1 Abbreviations used in this paper: CMJ, cortico medullary junction; DP, double positive; EtBr, ethidium bromide; fasL, fas ligand; FcR, Fc receptor; SP, single positive; TNFR, TNF receptor.


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