title: Rapamycin in combination with donor-specific CD4+CD25+Treg cells amplified in vitro might be realize the immune tolerance in clinical organ transplantation.
abstract: It is an urgent need to induce and keep the donor-specific immune tolerance without affecting the function of normal immune defense and immune surveillance in clinical organ transplantation. Large number of studies showed that both the establishment of donor-recipient chimerism and the application of antibodies or drugs could obtain the donor-specific immune tolerance in animal transplantation model. However, the former as treatment of clinical practice has a poor feasibility, the latter has a very low success rate in clinical organ transplantation. There is a group of naturally occurring CD4(+)CD25(+) regulatory T cells (Tregs) that mediate immune tolerance by suppressing alloreactive T cells in vivo. These cells are unable to curb the occurrence of allograft rejection owing their low content. And donor-specific Tregs amplified in vitro alone can not induce donor-specific immune tolerance for recipient. Rapamycin (RPM) as a proliferation signal inhibitor, studies have shown it can effectively inhibit allograft rejection and maybe contribute to induction of immune tolerance. But there exist still many dose-dependent adverse reactions which could prevent the establishment of immune tolerance and reduce the life quality of recipients in the clinical application of RPM. Therefore, we speculate a small amount of RPM combined with donor-specific Tregs amplified in vitro may be not only induce the achievement of donor-specific tolerance, but also reduce or eliminate the side effects of RPM in clinical organ transplantation.
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology of Health Ministry of China, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan Province, PR China.
authors.forename: Chuntao
authors.initials: C
authors.lastname: Zhang
authors.forename: Juan
authors.initials: J
authors.lastname: Shan
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Yuchuan
authors.initials: Y
authors.lastname: Huang
authors.forename: Li
authors.initials: L
authors.lastname: Feng
authors.forename: Dan
authors.initials: D
authors.lastname: Long
authors.forename: Shengfu
authors.initials: S
authors.lastname: Li
authors.forename: Quansheng
authors.initials: Q
authors.lastname: Li
authors.forename: Youping
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis; D003131:Combined Modality Therapy; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D016377:Organ Transplantation; D020123:Sirolimus / Q000627:therapeutic use*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D020123:Sirolimus