同种反应性自然杀伤细胞对小鼠单倍体骨髓移植后T细胞重建的影响

Effect of alloreactive natural killer cell on T-cell reconstitution after mouse haploidentical bone marrow transplantation

目的探讨同种反应性自然杀伤(NK)细胞对小鼠单倍体骨髓移植(BMT)后T细胞重建的可能影响。方法以(C57BL/6×BALB/c)BCF1(H-2d/b)为供鼠,BALB/c(H-2d)为受鼠,鼠龄6～8周,体质量16～20 g。建立小鼠单倍体BMT模型。根据移植物不同将实验分为单纯BMT组、非同种反应性NK(non-alloNK)细胞组、同种反应性NK(allo-NK)细胞组,移植后不同时间点以外周血CD3e的表达、外周血血清白细胞介素4(IL-4)、干扰素(IFN-γ)浓度等指标评价同种反应性NK细胞对T细胞重建的可能影响。结果移植后+10 d受鼠外周血CD3e的表达allo-NK组较non-alloNK组显著增高,分别为(16.58±5.77)%、(8.64±3.60)%,差异具有统计学意义(P<0.05)。+30 d时allo-NK组IL-4的浓度显著低于单纯BMT组,分别为(9.73±2.08)pg/mL、(12.44±1.57)pg/mL,差异具有统计学意义(P<0.05)。non-alloNK组IFN-γ的浓度显著高于单纯BMT组,分别为(98.78±33.07)pg/mL、(52.15±18.87)pg/mL,差异具有统计学意义(P<0.05)。结论同种反应性NK细胞用于单倍体BMT小鼠,可能促进T细胞的重建,体内诱导Th1免疫反应的偏移。

Objective To investigate the effect of alloreactive natural killer（NK） cells on T cell immune reconstitution in murine haploidentical bone marrow transplantation （BMT）. Methods The murine model of haploidentical BMT was established by （C57BL/6 × BALB/c） BCF1（H-2^d/b） mouse as the donor, and BALB/c（H-2^d） mouse as the recipient, aged 6 - 8 weeks, body weight 16 - 20 g. Recipient mice were divided into BMT group（no NK cells）, non-alloreactive NK cells（non- alloNK） group and alloreactive NK cells（allo-NK） group for different graft. The effect of adding alloreactive NK cell to graft was assessed by proportion of peripheral T cell, the interleukin 4（IL-4） and interferon-γ（IFN-γ） concentrations in the recipient peripheral blood after BMT. Results The proportion of recipient peripheral T cell in allo-NK group was significantly higher than that in non-alloNK group 10 days after BMT[（16.58 ± 5.77） % vs （8.64 ±3.60） %, P〈 0.05]. The IL-4 concentration in the recipient peripheral blood in allo-NK group was significantly lower than that in BMT group 30 days after BMT [（9.73 ± 2.08） pg/mL vs （12.44± 1.57） pg/mL, P 〈 0.05 ]. The IFN-γ concentration in the recipient peripheral blood in non-alloNK group was significantly higher than that in BMT group[（98.78 ＋_ 33.07） pg/mL vs （52.15 ~ 18.87） pg/mL, P 〈 0.05]. Conclusion It is demonstrated that alloreactive NK cells could promote peripheral T cell reconstitution and induce Thl immune response in murine haploidentical BMT.