[Studies on the induction of transplantation tolerance and immune reconstitution through combined strategies].
The induction of transplantation tolerance and the improvement of immune reconstitution after allogeneic bone marrow transplantation are the main research fields in the clinic organ transplantation and transplantation immunology. Over the past 5 years serial studies have been performed in our lab to induce robust transplantation tolerance by using combined strategies and improve the immune reconstitution of mice following allogeneic bone marrow transplantation by using gene-engineered bone marrow stromal cells. The results are encouraging. (1) The long-term survival of allografts was received by blockade of both CD28/B7 and CD40/CD40L or CD28/B7 and OX40/OX40L costimulation signals. In the case of blockade of both CD28/B7 and OX40/OX40L, the islet allograft survival was over 150 days compared to the control 14 days. (2) The CTLA4Ig-FasL fusion molecule expressed by adenoviral vector containing CTLA4Ig-FasL gene can prevent the autoimmune diabetes of mice and significantly prolong the survival time of cardiac allografts in rats, indicating that Fas-FasL-mediated apoptosis is able to enhance CTLA4Ig-induced transplantation tolerance. (3) In the time-window of peripheral tolerance induced by various methods, the systemic infusion of donor bone marrow cells and spleen cells obtained stable allogeneic mixed chimerism and robust transplantation tolerance. In the case of CTLA4Ig-FasL treatment combined with donor bone marrow cells more than 20% donor-origin blood cells chimerism, and more than 200 days prolonged skin allograft survival were obtained or received. (4) The murine bone marrow stromal cell line QXMSC1 transfected with IL-6 gene or IL-2+IL-3 genes significantly improved the immune reconstitution of mice following allogeneic bone marrow transplantation. Furthermore, It was observed that the mesenchymal stem cells transfected with IL-7 gene suppressed 90% of GVHD and expressed antileukemic effect, while accelerating immune reconstitution in mice following allogeneic bone marrow transplantation, which might be valuable in the clinic setting.
Xie
Shusheng
S
Department of Immunology, Peking University School of Basic Medical Sciences, Beijing 100083, China. Xiess@bjmu.edu.cn
Jin
Yongzhu
Y
Li
Ailing
A
Qin
Fenghua
F
Wang
Guangming
G
Ma
Jianbo
J
Hao
Jie
J
Gao
Xiang
X
D000818:Animals; D006085:Graft Survival / Q000276:immunology*; D006801:Humans; D018796:Immunoconjugates / Q000276:immunology; D051379:Mice; D016377:Organ Transplantation / Q000379:methods*; D051381:Rats; D018183:Transplantation Chimera / Q000276:immunology; D019172:Transplantation Conditioning / Q000379:methods; D023001:Transplantation Tolerance / Q000276:immunology*
D018796:Immunoconjugates