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Use of Rapamycin in the Induction of Tolerogenic Dendritic Cells

  • Chapter
Dendritic Cells

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 188))

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.

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Authors and Affiliations

  1. Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA

    Ryan Fischer

  2. Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA

    Heth R. Turnquist

  3. Department of Surgery, Mayo Clinic, Rochester, MN, 55905, USA

    Timuçin Taner

  4. University of Pittsburgh, W1544 Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA, 15213, USA

    Angus W. Thomson

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  1. Ryan Fischer
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  2. Heth R. Turnquist
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  3. Timuçin Taner
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  4. Angus W. Thomson
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Correspondence to Angus W. Thomson .

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Editors and Affiliations

  1. DIIID, King's College, London School of Medicine, Guy's Hospital, London, UK

    Giovanna Lombardi (Professor of Human Transplant Immunology MRC Centre in Transplantation Dep. of Nephrology and Transplantation) (Professor of Human Transplant Immunology MRC Centre in Transplantation Dep. of Nephrology and Transplantation)

  2. 5th Floor Hodgkin Building, School of Biomedical and Health Sciences, King's College London, London, SE1 1UL, United Kingdom

    Yanira Riffo-Vasquez (Research Fellow The Sackler Institute of Pulmonary Pharmacology Pharmaceutical Science Division) (Research Fellow The Sackler Institute of Pulmonary Pharmacology Pharmaceutical Science Division)

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Fischer, R., Turnquist, H.R., Taner, T., Thomson, A.W. (2009). Use of Rapamycin in the Induction of Tolerogenic Dendritic Cells. In: Lombardi, G., Riffo-Vasquez, Y. (eds) Dendritic Cells. Handbook of Experimental Pharmacology, vol 188. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-71029-5_10

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