Use of rapamycin in the induction of tolerogenic dendritic cells

Angus W. Thomson, Ryan Fischer, Heth R. Turnquist, Timuçin Taner

Research output: Chapter in Book/Report/Conference proceedingChapter

45 Scopus citations

Abstract

Rapamycin (RAPA), a macrocyclic triene antibiotic pro-drug, is a clinically-utilized 'tolerance-sparing' immunosuppressant that inhibits the activity of T, B, and NK cells. Furthermore, maturation-resistance and tolerogenic properties of dendritic cells (DC) can be supported and preserved by conditioning with RAPA. Propagation of murine bone marrow (BM)-derived myeloid DC (mDC) in clinically relevant concentrations of RAPA (RAPA-DC) generates phenotypically immature DC with low levels of MHC and significantly reduced co-stimulatory molecules (especially CD86), even when exposed to inflammatory stimuli. RAPA-DC are weak stimulators of T cells and induce hyporesponsiveness and apoptosis in allo-reactive T cells. An interesting observation has been that RAPA-DC retain the ability to stimulate and enrich the regulatory T cells (Treg). Presumably as a result of these properties, alloantigen (alloAg)-pulsed recipient-derived DC are effective in subverting anti-allograft immune responses in rodent transplant models, making them an attractive subject for further investigation of their tolerance-promoting potential.

Original languageEnglish (US)
Title of host publicationDendritic Cells
Pages215-232
Number of pages18
DOIs
StatePublished - 2009

Publication series

NameHandbook of Experimental Pharmacology
Volume188
ISSN (Print)0171-2004

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology, Toxicology and Pharmaceutics(all)

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    Thomson, A. W., Fischer, R., Turnquist, H. R., & Taner, T. (2009). Use of rapamycin in the induction of tolerogenic dendritic cells. In Dendritic Cells (pp. 215-232). (Handbook of Experimental Pharmacology; Vol. 188). https://doi.org/10.1007/978-3-540-71029-5-10