Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Department of Parasitology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
Infect Immun. 2018 Jul 23;86(8). doi: 10.1128/IAI.00147-18. Print 2018 Aug.
Interleukin 21 (IL-21) is a pleiotropic common cytokine receptor γ chain cytokine that promotes the effector functions of NK cells and CD8 T cells and inhibits CD8 T cell exhaustion during chronic infection. We found that the absolute number of short-lived effector CD8 T cells (SLECs) (KLRG1 CD127) decreased significantly in IL-21 receptor-deficient (IL-21R) mice during bacillus Calmette-Guérin (BCG) infection. Early effector CD8 T cells (EECs) (KLRG1 CD127) were normally generated in IL-21R mice after infection. Exhausted CD8 T cells (PD-1 KLRG1) were also normally generated in IL-21R mice after infection. Mixed bone marrow (BM) chimera and transfer experiments showed that IL-21R on CD8 T cells was essential for the proliferation of EECs, allowing them to differentiate into SLECs after BCG infection. On the other hand, the number of SLECs increased significantly after infection with recombinant BCG (rBCG) that secreted an antigen 85B (Ag85B)-IL-21 fusion protein (rBCG-Ag85B-IL-21), but the number of exhausted CD8 T cells did not change after rBCG-Ag85B-IL-21 infection. These results suggest that IL-21 signaling drives the differentiation of SLECs from EECs but does not inhibit the exhaustion of CD8 T cells following BCG infection in mice.
白细胞介素 21（IL-21）是一种多功能的共同γ链细胞因子，可促进 NK 细胞和 CD8 T 细胞的效应功能，并抑制慢性感染期间 CD8 T 细胞衰竭。我们发现，在卡介苗（BCG）感染期间，IL-21 受体缺陷（IL-21R）小鼠中短命效应 CD8 T 细胞（SLEC）（KLRG1 CD127）的绝对数量显着减少。感染后，IL-21R 小鼠中早期效应 CD8 T 细胞（EEC）（KLRG1 CD127）正常产生。感染后，IL-21R 小鼠中也正常产生衰竭的 CD8 T 细胞（PD-1 KLRG1）。混合骨髓（BM）嵌合体和转移实验表明，CD8 T 细胞上的 IL-21R 对于 EEC 的增殖是必需的，使它们能够在 BCG 感染后分化为 SLEC。另一方面，感染分泌抗原 85B（Ag85B）-IL-21 融合蛋白（rBCG-Ag85B-IL-21）的重组 BCG（rBCG）后，SLEC 的数量显着增加，但 rBCG-Ag85B-IL-21 感染后衰竭的 CD8 T 细胞数量没有变化。这些结果表明，IL-21 信号驱动 SLEC 从 EEC 分化，但不能抑制 BCG 感染后小鼠 CD8 T 细胞的衰竭。
