Intrinsic ability of GM + IL-4 but not Flt3L-induced rat dendritic cells to promote allogeneic T cell hyporesponsiveness

Aurele Taieb, Jeremy J. Breitinger, Jignesh V. Unadkat, William J. Shufesky, Adrian E. Morelli, Angus W. Thomson, W. P.Andrew Lee, Maryam Feili-Hariri

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

The influence of GM + IL-4 and Flt3 ligand (FL) on phenotype and function of BM-derived DC from Lewis rats was investigated. GM + IL-4-induced DC, despite expression of CD80/CD86, were less stimulatory than FL-induced DC that expressed low CD80/CD86 and were efficient stimulators of allogeneic T cells. GM + IL-4 DC were CD11b+ OX62lo, whereas FL DC were CD11blo OX62+. Following activation, GM + IL-4 DC produced IL-10 and IL-6, but no IL-12p70, and were resistant to further maturation. FL DC produced IL-12p70, IFN-α/β, IL-10 and IL-6 and underwent maturation. Repeated stimulation of T cells with GM + IL-4 DC inhibited proliferation, cytokine production and induced early T cell apoptosis. FL DC-activated T cells produced large amounts of IFN-γ/IL-10 and exhibited late T cell apoptosis/necrosis. In vivo, GM + IL-4 DC induced alloAg-specific hyporesponsiveness following T cell restimulation. These results demonstrate that GM + IL-4 DC display intrinsic regulatory properties, inducing passive-cell-death in T cells with potential for inactivation/regulation of alloreactive T cells in transplantation.

Original languageEnglish (US)
Pages (from-to)176-189
Number of pages14
JournalClinical Immunology
Volume123
Issue number2
DOIs
StatePublished - May 1 2007
Externally publishedYes

Keywords

  • Bone marrow
  • Cytokines
  • Dendritic cells
  • Hyporesponsiveness
  • Passive-cell-death
  • Rat

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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