ABSTRACT
Objective To explore the effects of iPS cells-derived chimeric thymus transplantation on T cells reconstitution and graft versus host disease of murine after allo-BMT. Methods iPS cells-derived chimeric thymus was grafted under the renal capsules of mice after allogeneic IBM-BMT. The mice were divided into three groups:IBM-BMT group, IBM-BMT+TT group and IBM-BMT+DLI group. Four weeks after BMT, T lymphocyte subsets in the peripheral blood were analyzed by flow cytometry, the degree and pathological examination of GVHD were observed, respectively. Results Percentage of CD8+T cells in IBM-BMT group, IBM-BMT+TT group and IBM-BMT+DLI group was(5.52 ± 0.83)%,(11.10 ± 1.49)%and(8.49 ± 0.82)%respectively, there was signifi-cant difference between pairwise comparisons(P<0.05), and percentage of CD4 + T cells of the peripheral blood in IBM-BMT+TT group(9.60 ± 0.69)%was significantly higher than IBM-BMT group(6.42 ± 1.40)%and IBM-BMT+DLI group(8.07 ± 0.65)%(P<0.05) . IBM-BMT group and IBM-BMT+TT group showed less clinical and histopathological scoring of GVHD than IBM-BMT + DLI group. Conclusion iPS cells-derived chimeric thymus transplantation could effectively accelerate T cells reconstitution and prevent GVHD after allo-BMT.
ABSTRACT
Objective To study the effects of thymus transplantation(TT)combined with CD4--DLI on T cell reconstitution after allogeneic hematopoietic stem cell transplantation(allo-HSCT). Methods BALB/c mice were randomly divided into three groups:hematopoietic stem cell transplantation (HSCT group),hematopoietic stem cell transplantation combined with thymus transplantation(TT group)and hematopoietic stem cell transplanta-tion combined with thymus transplantation plus CD4+ T cell-depleted lymphocyte infusion(CD4--DLI group). On day-1,the mice were treated with the lethal dose of radiotherapy. On day 0,C57BL/6 mice were used as donor for hematopoietic stem cell transplantation. The mice were sacrificed on 5 days,2 weeks,4 weeks and 3 months after transplantation,respectively. The peripheral blood and spleen cells of mice were collected for determinations of T cell surface antigen,T cell receptor,naive T cells and intracellular cytokines. HE staining was used to assess the development of donor thymus. Results TT and CD4--DLI did not impair each other′s effects on T cell reconstitu-tion. TT combined with CD4--DLI increased the number of T cell reconstruction. CD4--DLI promoted the effect of TT on enlargement naive CD4+and CD8+T cell pool. Combination of TT and CD4--DLI enhanced the cytokine pro-duction of T cells. Conclusion TT combined with CD4--DLI had no side effects on TCR repertoire and thymus. Conclusion TT combined with CD4--DLI can enhance the reconstitution of T cell number and function via thymus dependent and thymus independent mechanism.
ABSTRACT
Objective To explore the effect of fetal thymus transplantation on enhancing the immunity of patients with late-stage malignant tumors. Methods The whole thymus of 24～32 weeks fetus was transplanted into the forearm of the patients with late-stage milignant tumors by microvascular surgery. The levels of serum IgA,IgG and IgM were measured before and at the third, 6th and 12th months after operation. No immunosuppressive regimen was performed in all the patients after operation. The follow-up period was 1 to 2 years. Results The clinical symptoms of all the patients improved after treatment, and no rejection reaction occurred. The levels of serum IgA,IgG and IgM significantly increased 3,6 and 12 months after treatment(t≥4.23,P