白细胞介素21和白细胞介素15对同种异体抗原刺激的体外扩增CD8 + T细胞的不同作用。
Different Effects of Interleukin 21 and Interleukin 15 on In Vitro Expanded CD8+ T Cells Stimulated by Alloantigen.
作者信息
Zhang Hua, Liu Yanjun, Feng Fu, Liu Guihuan, Feng Xiaoqiang, Zhang Zedan, Xie Lu, Liu Jiumin, Yu Yuming
机构信息
Department of Urology, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.
Department of Immunology, School of Basic Medical Science, Southern Medical University, Guangzhou, China.
出版信息
Transplant Proc. 2019 Dec;51(10):3456-3462. doi: 10.1016/j.transproceed.2019.08.034. Epub 2019 Nov 14.
OBJECTIVE
To investigate the effects of IL (interleukin) 21 on CD8 T cells stimulated by alloantigen in the presence of IL-15 in vitro.
METHODS
CD8 T cells sorted with MicroBeads from fresh human peripheral blood mononuclear cells were cocultured with antigen-presenting cells derived from HLA-A, -B, and -DR full-mismatched individuals for 9 days without any cytokines, in the presence of IL-15, IL-21, and IL-15 combined with IL-21, respectively. The proliferation and phenotypic characteristics of CD28 and CD28 subsets were measured after 9 days of culture.
RESULTS
The proliferation of CD8 T cells can be promoted either by IL-15 alone or in combination with IL-21 compared with IL-21. Cells expanded in the presence of IL-15 are mainly CD8CD28 T cells, while those expanded in the presence of IL-15 combined with IL-21 are mostly CD8CD28 T cells. In the presence of IL-15, most CD8CD28 T cells shifted to CD8CD28 T cells during the process of proliferation, but In the presence of IL-15 combined with IL-21, CD8CD28 T cells didn't shift to CD8CD28 T cells during proliferation, moreover, CD8CD28 T cells cannot transform in reverse to CD8CD28 T cells. IL-21 combined with IL-15 can promote the expression of granzyme B and perforin in CD8CD28 and/or CD8CD28 T cells compared with IL-15 alone.
CONCLUSION
IL-21 cannot promote the proliferation of CD8 T cells under allogeneic stimulation unless combined with IL-15. IL-21 prevents the loss of CD28 molecules caused by IL-15 but cannot promote its re-expression in CD28 T cells. CD8 T cells expanded by IL-21 combined with IL-15 is characterized by cytotoxic phenotype.
目的
研究白细胞介素（IL）-21在体外IL-15存在的情况下对同种异体抗原刺激的CD8⁺ T细胞的影响。
方法
用微珠从新鲜人外周血单个核细胞中分选的CD8⁺ T细胞，分别与来自HLA-A、-B和-DR完全不匹配个体的抗原呈递细胞共培养9天，分别在无任何细胞因子、IL-15、IL-21以及IL-15与IL-21联合存在的情况下培养。培养9天后检测CD28⁺和CD28⁻亚群的增殖及表型特征。
结果
与IL-21相比，IL-15单独或与IL-21联合均可促进CD8⁺ T细胞的增殖。在IL-15存在下扩增的细胞主要是CD8⁺CD28⁺ T细胞，而在IL-15与IL-21联合存在下扩增的细胞大多是CD8⁺CD28⁻ T细胞。在IL-15存在下，大多数CD8⁺CD28⁺ T细胞在增殖过程中转变为CD8⁺CD28⁻ T细胞，但在IL-15与IL-21联合存在时，CD8⁺CD28⁺ T细胞在增殖过程中不会转变为CD8⁺CD28⁻ T细胞，而且，CD8⁺CD28⁻ T细胞也不能逆向转变为CD8⁺CD28⁺ T细胞。与单独使用IL-15相比，IL-21与IL-15联合可促进CD8⁺CD28⁺和/或CD8⁺CD28⁻ T细胞中颗粒酶B和穿孔素的表达。
结论
IL-21在同种异体刺激下不能促进CD8⁺ T细胞增殖，除非与IL-15联合。IL-21可防止IL-15导致的CD28分子丢失，但不能促进其在CD28⁻ T细胞中的重新表达。IL-21与IL-15联合扩增的CD8⁺ T细胞具有细胞毒性表型特征。
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