The Journal of Experimental Medicine
Randox clinical diagnostic solutions
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 19 February 2002. doi:10.1084/jem.20011662
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 Mailliard, R. B.
Right arrow Articles by Kalinski, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mailliard, R. B.
Right arrow Articles by Kalinski, P.
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?
© Rockefeller University Press, 0022-1007/2002/2/473/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 4, February 18, 2002 473-483

Original Article

 Complementary Dendritic Cell–activating Function of CD8+ and CD4+ T Cells : Helper Role of CD8+ T Cells in the Development of T Helper Type 1 Responses



Robbie B. Mailliard1, Shinichi Egawa1, Quan Cai1, Anna Kalinska1, Svetlana N. Bykovskaya1, Michael T. Lotze1, Martien L. Kapsenberg3, Walter J. Storkus1,2 and Pawel Kalinski1,2

1 Department of Surgery, University of Pittsburgh
2 University of Pittsburgh Cancer Institute, Pittsburgh, PA 15261
3 Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands

Address correspondence to P. Kalinski, Department of Surgery, University of Pittsburgh, W1540 BST, 200 Lothrop St., Pittsburgh, PA 15261. Phone: 412-624-6451; Fax: 412-624-1172; E-mail: KalinskiP{at}msx.upmc.edu

Dendritic cells (DCs) activated by CD40L-expressing CD4+ T cells act as mediators of "T helper (Th)" signals for CD8+ T lymphocytes, inducing their cytotoxic function and supporting their long-term activity. Here, we show that the optimal activation of DCs, their ability to produce high levels of bioactive interleukin (IL)-12p70 and to induce Th1-type CD4+ T cells, is supported by the complementary DC-activating signals from both CD4+ and CD8+ T cells. Cord blood– or peripheral blood–isolated naive CD8+ T cells do not express CD40L, but, in contrast to naive CD4+ T cells, they are efficient producers of IFN-{gamma} at the earliest stages of the interaction with DCs. Naive CD8+ T cells cooperate with CD40L-expressing naive CD4+ T cells in the induction of IL-12p70 in DCs, promoting the development of primary Th1-type CD4+ T cell responses. Moreover, the recognition of major histocompatibility complex class I–presented epitopes by antigen-specific CD8+ T cells results in the TNF-{alpha}– and IFN-{gamma}–dependent increase in the activation level of DCs and in the induction of type-1 polarized mature DCs capable of producing high levels of IL-12p70 upon a subsequent CD40 ligation. The ability of class I–restricted CD8+ T cells to coactivate and polarize DCs may support the induction of Th1-type responses against class I–presented epitopes of intracellular pathogens and contact allergens, and may have therapeutical implications in cancer and chronic infections.

Key Words: T helper subsets • dendritic cells • maturation • IL-12 • CD8+ T cells


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