TY - CHAP
T1 - Use of rapamycin in the induction of tolerogenic dendritic cells
AU - Thomson, Angus W.
AU - Fischer, Ryan
AU - Turnquist, Heth R.
AU - Taner, Timuçin
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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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U2 - 10.1007/978-3-540-71029-5-10
DO - 10.1007/978-3-540-71029-5-10
M3 - Chapter
C2 - 19031028
AN - SCOPUS:60549107773
SN - 9783540710288
T3 - Handbook of Experimental Pharmacology
SP - 215
EP - 232
BT - Dendritic Cells
ER -