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Blocking of the B7-CD28 Pathway Increases the Capacity of FasL+ (CD95L+) Dendritic Cells to Kill Alloactivated T Cells

  • Lina Lu
  • Shiguang Qian
  • Thomas E. Starzl
  • David H. Lynch
  • Angus W. Thomson
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 417)

Abstract

Dendritic cells (DC) are antigen presenting cells of hemopoietic origin, uniquely well-equipped to activate naive T cells.1 Evidence also exists however, for DC tolerogenicity.2 During primary activation, mature T cells change from an activation-induced cell death (AICD) -resistant to an AICD-sensitive phenotype.3 The complete molecular basis for this transition remains to be determined, but CD95 (Fas/Apo-1) and CD95L (Fas ligand; FasL) appear to play an important role in the homeostatic regulation of T cell responses.4 It seems that CD95L can mediate opposite effects (T cell activation or apoptosis) depending on the state of activation of the responding T cells. Previously, we have shown that mouse bone marrow (BM)-derived DC progenitors deficient in expression of cell surface costimulatory molecules B7-1 (CD80) and B7-2 (CD86) are capable of inducing alloantigen-specific T cell hyporesponsiveness5 and prolonging allograft survival.6 Others have shown recently that a major subpopulation of freshly-isolated mouse lymphoid tissue DC is FasL+, and can induce apoptosis in allogeneic T cells.7 In the course of studies on DC propagated in vitro from mouse BM, we observed that these cells expressed Fas L. Our aim was to determine whether these cells could induce T cell apoptosis and whether costimulatory molecule expression could affect this activity.

Keywords

Dendritic Cell Mouse Bone Marrow FasL Expression CD28 Costimulation Mixed Leukocyte Reaction 
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

  • Lina Lu
    • 1
    • 2
  • Shiguang Qian
    • 1
    • 2
  • Thomas E. Starzl
    • 1
    • 2
  • David H. Lynch
    • 4
  • Angus W. Thomson
    • 1
    • 2
    • 3
    • 5
  1. 1.Thomas E. Starzl Transplantation InstituteUSA
  2. 2.Department of SurgeryUniversity of PittsburghPittsburghUSA
  3. 3.Department of Molecular Genetics and BiochemistryUniversity of PittsburghPittsburghUSA
  4. 4.Immunex Research and Development CorporationSeattleUSA
  5. 5.Thomas E. Starzl Transplantation Institute, 15th Floor, Biomedical Science TowerUniversity of Pittsburgh Medical CenterPittsburghUSA

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