Dendritic cells genetically engineered to express Fas ligand induce donor-specific hyporesponsiveness and prolong allograft survival

被引:192
作者
Min, WP
Gorczynski, R
Huang, XY
Kushida, M
Kim, P
Obataki, M
Lei, J
Suri, RM
Cattral, MS
机构
[1] Toronto Hosp, Dept Surg, Toronto, ON M5G 2C4, Canada
[2] Toronto Hosp, Multiorgan Transplant Program, Toronto, ON M5G 2C4, Canada
[3] Univ Toronto, Res Inst, Toronto, ON, Canada
[4] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada
关键词
D O I
10.4049/jimmunol.164.1.161
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Polarization of an immune response toward tolerance or immunity is dictated by the interactions between T cells and dendritic cells (DC), which in turn are modulated by the expression of distinct cell surface molecules, and the cytokine milieu in which these interactions are taking place. Genetic modification of DC with genes coding for specific immunoregulatory cell surface molecules and cytokines offers the potential of inhibiting immune responses by selectively targeting Ag-specific T cells. In this study, the immunomodulatory effects of transfecting murine bone marrow-derived DC with Fas ligand (FasL) were investigated. In this study, we show that Fast transfection of DC markedly augmented their capacity to induce apoptosis of Fas(+) cells. FasL-transfected DC inhibited allogeneic MLR in vitro, and induced hyporesponsiveness to alloantigen in vivo. The induction of hyporesponsiveness was Ag specific and was dependent on the interaction between Fast on DC and Fas on T cells. Finally, we show that transfusion of FasL-DC significantly prolonged the survival of fully MHC-mismatched vascularized cardiac allografts, Our findings suggest that DC transduced with,FasL may facilitate the development of Ag-specific unresponsiveness for the prevention of organ rejection. Moreover, they highlight the potential of genetically engineering DC to express other genes that affect immune responses.
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页码:161 / 167
页数:7
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