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Liver-derived DEC205+B220+CD19- dendritic cells regulate T cell responses.

L Lu1, C A Bonham, X Liang

  • 1Thomas E. Starzl Transplantation Institute and Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. lul@msx.upmc.edu

Journal of Immunology (Baltimore, Md. : 1950)
|June 8, 2001
PubMed
Summary

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Researchers identified a novel liver cell population that suppresses T cell proliferation and promotes allograft survival. These cells, characterized by DEC-205 and B220 expression, induce T cell apoptosis and a regulatory cytokine profile, offering potential therapeutic strategies for transplantation.

Area of Science:

  • Immunology
  • Cell Biology
  • Transplantation Immunology

Background:

  • Liver leukocytes play a role in immune responses.
  • Nonparenchymal liver cells can be cultured to yield distinct cell populations.

Purpose of the Study:

  • To characterize a novel population of liver-derived cells with unique immunophenotype and function.
  • To investigate the role of these cells in T cell differentiation and allograft survival.

Main Methods:

  • Culture of mouse liver nonparenchymal cells with IL-3 and anti-CD40 mAb.
  • Flow cytometry analysis for surface markers (DEC-205, B220, CD11c, CD19, etc.).
  • Mixed lymphocyte reaction (MLR) to assess T cell proliferation and apoptosis, cytokine analysis, and in vivo allograft survival studies.

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Main Results:

  • A novel cell population, DEC-205(bright)B220+CD11c-CD19-, was propagated from mouse liver.
  • These cells induced T cell apoptosis in MLR, which was reversed by caspase inhibition.
  • T cells stimulated by these cells produced IL-10 and IFN-gamma, resembling T regulatory type 1 cells.
  • In vivo administration of these cells prolonged cardiac allograft survival in an alloantigen-specific manner.

Conclusions:

  • Liver-derived DEC-205+B220+CD19- cells possess unique immunophenotypic and functional characteristics.
  • These cells exhibit immunosuppressive properties, inducing T cell apoptosis and promoting regulatory cytokine production.
  • This cell population holds potential for therapeutic applications in preventing allograft rejection.