title: Donor-Specific Regulatory T Cells Acquired from Tolerant Mice Bearing Cardiac Allograft Promote Mixed Chimerism and Prolong Intestinal Allograft Survival.
abstract: The induction of donor-specific transplant tolerance has always been a central problem for small bowel transplantation (SBT), which is thought to be the best therapy for end-stage bowel failure. With the development of new tolerance-inducing strategies, mixed chimerism induced by co-stimulation blockade has become most potent for tolerance of allografts, such as skin, kidney, and heart. However, a lack of clinically available co-stimulation blockers has hindered efficient application in humans. Furthermore, unlike those for other types of solid organ transplantation, strategies to induce robust mixed chimerism for intestinal allografts have not been fully developed. To improve current mixed chimerism induction protocols for future clinical application, we developed a new protocol using donor-specific regulatory T (Treg) cells from mice with heart allograft tolerance, immunosuppressive drugs which could be used clinically and low doses of irradiation. Our results demonstrated that donor-specific Treg cells acquired from tolerant mice afterin vitroexpansion generate stable chimerism and lead to acceptance of intestinal allograft. Increased intragraft Treg cells and clonal deletion contribute to the development of SBT tolerance.
authors.affiliation: Department of General Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School , Nanjing , China.
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Shen
authors.affiliation: Department of Rehabilitation Medicine, PLA Army General Hospital , Beijing , China.
authors.forename: Jin-Peng
authors.initials: JP
authors.lastname: Jiang
authors.affiliation: Division of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University , Xi'an , China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Division of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University , Xi'an , China.
authors.forename: Wei-Zhong
authors.initials: WZ
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School , Nanjing , China.
authors.forename: Wen-Xian
authors.initials: WX
authors.lastname: Guan
authors.affiliation: Department of General Surgery, PLA Army General Hospital , Beijing , China.
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Du
keywords: bone marrow transplantation; donor-specific regulatory T cells; mixed chimerism; small bowel transplantation; transplantation tolerance