期刊
CURRENT OPINION IN ORGAN TRANSPLANTATION
卷 17, 期 2, 页码 155-161出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MOT.0b013e3283508e17
关键词
rejection; T-regulatory cells; tolerance; xenotransplantation
资金
- Swiss National Research Foundation [3200BO-102134, 32323B-111370/32003B-111371, 320030-138376]
- Desiree Niels YDE
- Insuleman
- E. L. Schmidheiny
- Faculty of Biology and Medicine of Lausanne University
- Fondation Medi-CAL Futur
- Hans Wilsdorf
- Swiss National Science Foundation (SNF) [320030_138376] Funding Source: Swiss National Science Foundation (SNF)
Purpose of review Immunological barriers still preclude clinical xenotransplantation. The protective role of CD4(+)CD25(+)Foxp3(+) T-regulatory cells (Treg) in allotransplantation is well described and, therefore, could represent a promising therapeutical tool for xenotransplantation. This review addresses the latest findings on Treg in xenotransplantation research. Recent findings In vivo, costimulation blockade-based strategies including anti-CD154 monoclonal antibodies (mAbs) in combination with rapamycin or anti-LFA-1 mAb prolonged both concordant and discordant islets xenografts survival in a Treg-dependent manner. In vitro, IL-10 secretion was shown to be critical for the suppression of xenogeneic responses mediated by Treg. Moreover, transgenic expression of inducible costimulator-immunoglobulin or PD-L1 on porcine endothelial cells inhibited human T-cell proliferation in vitro and was associated with the induction of Treg and IL-10 secretion. CXCR3 mediated the recruitment of Treg to pig endothelium. Finally, the recruitment of human Treg was enhanced by the immobilization of human CCL17 on pig endothelium. Summary There is increasing evidence for the potential of CD4(+)CD25(+)Foxp3(+) Treg to protect xenografts. Induction of Treg in recipients and/or recruitment of human Treg to pig endothelium may represent novel strategies to prevent cell-mediated rejection in pig-to-human xenotransplantation.
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