Influence of the lentiviral vectors mediated mouse genetic engineering Tr after allogeneic bone marrow transplantation in mice
10.3760/cma.j.issn.0254-5101.2010.07.016
- VernacularTitle:慢病毒载体介导的鼠基因工程调节性T细胞对小鼠移植物抗宿主病的作用研究
- Author:
Jiang CAO
;
Li LI
;
Chong CHEN
;
Lingyu ZENG
;
Zhenyu LI
;
Xiuying PAN
;
Kailin XU
- Publication Type:Journal Article
- Keywords:
Bone marrow transplantation;
T lymphocytes,regulatory;
Graft-versus-host disease;
Lentiviral vector
- From:
Chinese Journal of Microbiology and Immunology
2010;30(7):650-654
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the influence of the lentiviral vectors mediated mouse genetic engineering regulatory T cells(Tr) infused after allogeneic bone marrow transplantation(allo-BMT) on graft-versushost disease(GVHD) in mice. Methods Lentivirus-mediated expression of forkhead box P3 (Foxp3) converted CD4 + CD25 - T cells from BALB/c mice into engineered Tr in vitro. An allo-BMT model of BALB/c→C57BL/6 mice was established. After irradiation, the recipients were injected with donor cells along with genetic engineering Tr. Survival time, histopathological analysis, serum levels of inflammatory cytokines were observed after allo-BMT. Results The mean survival times in radiation group, transplantation control group, engineering Tr group and empty vector control group were ( 8.8 ± 0.6 ) d, ( 36.7 ± 2.5 ) d, ( 51.6 ± 4.0 ) d and ( 34.1 ± 2. 3 ) d. The survival time in engineering Tr group was significantly increased as compared to other groups as judged by the log-rank test ( P ＜0.05 ). Histopathological analysis in several target organs( skin, liver and small intestine) confirmed the presence of severe GVHD in transplantation control group and empty vector control group. No histological signs of GVHD were observed in recipients in engineering Tr group. The serum levels of IFN-γ, IL-2 and TNF-α were all increased after transplantation in above groups. The peaks of concentrations of IFN-γ, IL-2 and TNF-α in engineering Tr group were significantly decreased compared to transplantation control group and empty vector control group at day 21 ( P ＜ 0. 05 ). Conclusion Co-injection of genetic engineering Tr can efficiently prevent recipients from lethal GVHD during allo-BMT in mice by reducing the serum levels of inflammatory cytokines.
