The potential association of CMV-specific CD8+ T lymphocyte reconstitution with the risk of CMV reactivation and persistency in post allogeneic stem cell transplant patients.

OBJECTIVES: development of cytomegalovirus (CMV)-specific CD8+ T cell response is crucial in preventing symptomatic CMV infection specially, in stem cell transplant (SCT) patients. The aim of this study was to evaluate CMV-specific CD8+ T cell reconstitution in allogeneic SCT recipients and to study the possible association between CMV-specific CD8+ T cell recovery with protection from CMV reactivation and persistency. METHODS: Human leuKocyte antigen (HLA)-tetramers were used for CMV-specific CD8+ cell quantitation by Flow cytometry in twenty post-allogeneic SCT patients. RESULTS: Nine patients (45%) developed rapid recovery of CMV-specific CD8+ cells, among them; 7 patients (78%) had no CMV reactivation in the first 95 days post-transplant. Five patients had developed persistent CMV viremia; all of them had not developed CMV-specific CD8+ recovery till day 95 post-transplant. Patients with persistent CMV viremia had a statistically significant lower means of CMV-specific CD8+ percent and absolute count compared to those without persistent viremia (p = .001, .015), respectively. DISCUSSION: The incidence of CMV reactivation and persistency was higher among patients with delayed CMV-specific CD8+ reconstitution in the first 95 days post-transplant. CONCLUSION: CMV-specific CD8+ cells can help in categorizing patients into risk groups: (early recovery/low risk) and (delayed recovery/increased risk), this tool may guide clinicians in the selection of patients who may profit from prophylactic antiviral therapy and frequent viral monitoring.

Induced Pluripotent Stem Cells-derived chimeric Thymus transplantation enhances T cells Reconstitution and prevents GVHD in Murine after allogeneic Bone Marrow Transplantation / 实用医学杂志

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.

Establishment of a animal model of allogeneic bone marrow transplantation plus thymic epithelial cells transplantation / 中华器官移植杂志

Objective To explore the establishment of animal model of allogeneic bone marrow transplantation plus thymic epithelial cells transplantation,and then examine the feasibility and effects of thymic epithelial cells transplantation applied in allogeneic bone marrow transplantation.Methods One day before transplantation the recipient BALB/C mice were given total-body irradiation,then transplanted with bone marrow cells from donor C57BL/6 mice and thymic epithelial cells from E14-16 embryonic thymus of donor C57BL/6 mice.In order to explore the appropriate irradiation dose,we set up three different dose groups:7 Gy;6.5 Gy;6 Gy.The recipient mice transplanted with BMT plus TCT served as experimental group,and those transplanted with BMT only served as control group (n =8 each).Then in vivo imaging in mammals was done to observe the thymic epithelial cells transplantation.Thymus index was measured.The thymus in each group was collected for histological examination and immunohistochemical staining of K5 and K8.Flow cytometry was used to examine the T cells subsets in peripheral blood of recipient mice 4 weeks after thymus transplantation.Results The recipient mice with 6.0 Gy TBI had long-term survival but implantation was done unsuccessfully,and those with 6.5 Gy had lower survival rate but implantation was done successfully.6.5 Gy was the minimum lethal dose and could be used as the appropriate irradiation does in this study.In vivo imaging in mammals detecting system showed the experimental group obvious fluorescent signals could be detected in the experimental group,but no fluorescence was found in the control group.Four weeks after transplantation,the thymus was bigger and thymus index was higher in the experimental group than in the control group.And the chiemra thymus of the experimental group also had normal cortex and medulla histological structure.Four weeks after transplantion,the percentages of CD4+ and CD8+ T cells of the peripheral blood in experimental group were significantly higher than in control group (P＜ 0.05).Conclusion Thymic epithelial cells can be transplanted in the thymus of the recipient mice with allogeneic bone marrow transplantation and promote the reconstitution of T lymphocytes of peripheral blood in the recipient mice.