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Activation of Dendritic Cells by Surrogate T Cell Interactions Leads to Enhanced Costimulation, Secretion of TH1-Associated Cytokines, and CTL Inductive Capacity

  • Cara C. Wilson
  • Thomas Tueting
  • Debora Ma
  • Cathy Haluszczak
  • Michael Lotze
  • Walter Storkus
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 417)

Abstract

Dendritic cells (DC), as professional antigen presenting cells (APC), have the capacity to capture antigen and migrate to lymphoid organs, where antigen presentation to and priming of naive T cells takes place (reviewed in 1). It is currently believed that effective induction of antigen-specific T cell responses requires a dynamic dialogue of multiple, sequential interactions between the DC as APC and a given T cell clone in order to prime the cell for expansion and effector function. The first interaction (signal 1) is felt to involve the MHC I/II-peptide on APC with the T cell receptor (TCR) on the effector lymphocyte, with a second signal being the costimulatory interaction between CD80 (B7.1)/CD86(B7.2) on DC with CD28 on the T cell. Signals 1 and 2 combine to activate the T cell, upregulating the expression of CD4OL which can interact with DC-expressed CD40 (reviewed in 2). This DC-T cell interaction results in the generation of an antigen-specific T cell responses. The ability of DC to prime naive T cells has been attributed to several factors, most notably the high levels of expression of MHC and costimulatory molecules such as B7.1 and B7.2. It has also been shown that DC are capable of producing several cytokines, among them IL-12, a cytokine critical for the development of Thl responses (3,4). Recently, ligation of CD40 on both human (5) and murine (6) DC has been reported to result in the upregulation of costimulatory molecules and the induction of IL-12. These findings suggest that the interaction of T cells with DC result in signals to DC which are critical for induction of the cellular immune response. Whereas many of the signals required by T cells for activation and proliferation have been described, the signaling requirements for optimal DC activation remain poorly defined.

Keywords

Dendritic Cell Antigen Present Cell Costimulatory Molecule Dendritic Cell Activation Dendritic Cell Culture 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Cara C. Wilson
    • 1
  • Thomas Tueting
    • 2
  • Debora Ma
    • 2
  • Cathy Haluszczak
    • 2
  • Michael Lotze
    • 2
  • Walter Storkus
    • 2
  1. 1.Department of MedicineUniversity of Pittsburgh Medical Center and the University of Pittsburgh Cancer InstitutePittsburghUSA
  2. 2.Department of SurgeryUniversity of Pittsburgh Medical Center and the University of Pittsburgh Cancer InstitutePittsburghUSA

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