期刊
TRANSPLANT INTERNATIONAL
卷 23, 期 12, 页码 1293-1300出版社
WILEY
DOI: 10.1111/j.1432-2277.2010.01130.x
关键词
cytotoxic effector cells; PD-1; PD-ligands; xenotransplantation
资金
- Deutsche Forschungsgemeinschaft [FOR 535]
P>Cellular rejection is a relevant hurdle for successful pig-to-primate xenotransplantion. We have shown previously that the induction of a human anti-pig T cell response (in vitro activation of CD4+ T cells) can be suppressed by the overexpression of human negative costimulatory ligands (e.g. programmed death receptor ligand, PD-L1) on pig antigen presenting cells. Here, we asked whether PD-L1 mediated enhancement of negative signaling might also be efficient during the effector phase of human anti-pig cellular immune responses. The porcine B-cell line L23 was transfected with human PD-L1, and clones were selected stably expressing PD-L1 with low, medium, or high density. Mock-transfected L23 cells were effectively lysed by human cytotoxic effector cells (IL-2 activated CD8+ T cells and CD56+ cells). The lytic potential of the effectors decreased with increasing levels of PD-L1 and was reduced by about 50% in L23-PD-Lhigh targets. A proportion of activated CD8+ effector cells underwent apoptosis when exposed to PD-L1 expressing L23 cells. These data suggest that the overexpression of PD-L1 on target cells may (a) trigger negative signals in effector cells that prevent the release of cytolytic molecules and/or (b) induce apoptosis in the attacking effector cells thereby protecting targets from destruction.
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