| Objective:(1) To detect CD4+CD25+CD127-T cells (Tregs) from DC-CIK, whichwere infused to patients with high-risk or refractory hematologic malignancies afterallogeneic hematopoietic stem cell transplantation(allo-HSCT) and to explore the functionof them, then to further discuss the relationship between different proportions of Tregs inDC-CIK and the occurrence of acute graft versus host disease(aGVHD), recurrence andsurvival.(2) To discuss the relationship between Tregs,Tim3and aGVHD by detectingproportions of Tregs and expression of Tim3in patients’peripheral blood.Methods:(1) Detected the percentage of Tregs in DC-CIK which were infused topatients with high-risk or refractory hematologic malignancies after allo-HSCT by flowcytometry.(2) Compared the occurrence of aGVHD, recurrence and survival with patientswho developed aGVHD but without DC-CIK infusion.(3) Sorted Tregs from DC-CIK byflow cytometry, using MTT assay and mixed lymphocyte reaction to research the inhibitionfunction of Tregs from DC-CIK in vitro.(4) Detected the proportions of Tregs by flowcytometry in patients with and without aGVHD, respectively.(5) Detected the expressionof Tim3on CD4+T cells, CD8+T cells, CD3-CD56+cells and CD4+CD25+T cells in patients withor without aGVHD, respectively.Results:(1)32patients with high-risk or refractory hematologic malignancies weretreated with DC-CIK after allo-HSCT.25cases of DC-CIK were donor-derived and7cases were receptor-derived.(2) When the percentage of Tregs in DC-CIK was less than5%, we defined as low proportion group, while high proportion group was defined whenthe percentage was more than10%.5%-10%was defined as middle proportion group.10cases were in low proportion group,16cases in middle proportion group and6cases in high proportion group.(3) The inhibition function was strongest when the ratio of Tregsand effective cells was1.3:1.(4) All patients were follow-up from December2012to July1,2013. The media follow-up was13.7(2-19.7) months.4/32(12.5%) patients with DC-CIKtreatment developed I-II aGVHD and3of them were in low proportion group,1in middleproportion group.10/27(37.03%) patients without DC-CIK treatment developed aGVHD.7of them developed I-II aGVHD and3developed III-IV. The incidence and degree of aGVHD inDC-CIK treatment group was significantly lower than none DC-CIK treatment group (P<0.05).7/32(21.88%) patients with DC-CIK treatment occurred recurrence and1of them was in lowproportion group,3in middle proportion group,2in high proportion group.8/27(29.63%)patients without DC-CIK treatment occurred recurrence. The ratio of recurrence between the two groupswas no significantly difference(P>0.05). The overall survival (OS) at2years was70.31%and52.37%,respectively and the disease-free survival (DFS) at2years was64.52%and53.84%, respectively.(5)The percentage of Tregs in patients with aGVHD was lower than patients without aGVHD (P<0.05).(6)The Tim3expression on CD4+T cells, CD8+T cells and CD4+CD25+T cells were higher inpatients with aGVHD than without aGVHD (P<0.05). While the expression was no significantlydifference in CD3-CD56+cells between the two groups(P<0.05).Conclusion:(1) Tregs in DC-CIK infusion play a critical role in immunosuppressive.DC-CIK infusion after allo-HSCT can reduce the incidence of aGVHD and do not influence the effectof graft versus leukemia (GVL) at the same time, thus being a promising method to improve the curerate of leukemia and providing a novel approach to cell biology treatment.(2) Tregs negatively regulateimmune reaction post allo-HSCT on the occurrence and progress of aGVHD while Tim3can promotesthe occurrence and progress of aGVHD through positively regulating immune reaction. Further researchwill be needed to provide approach to reduce recurrence of aGVHD and gain more methods on thepreventation and treatment of aGVHD. |
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