CD1d-restricted NKT cells contribute to the age-associated decline of T cell immunity
CD1d-restricted NKT cells contribute to the age-associated decline of T cell immunity
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DOI：
10.4049/jimmunol.175.5.3102
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发表时间：
2005-09-01
影响因子：
4.4
通讯作者：
Kovacs, EJ
中科院分区：
文献类型：
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作者：
Faunce, DE;Palmer, JL;Kovacs, EJ
已知 NKT 细胞在耐受、自身免疫和抗肿瘤免疫过程中调节效应 T 细胞免疫。 NKT 细胞数量或功能是否发生与年龄相关的变化仍不清楚。在这里，我们研究了年轻小鼠与老年小鼠（3 个月龄与 22 个月龄）小鼠是否具有不同数量的 CD1d 限制性 NKT 细胞，以及体内 CD1d 激活 NKT 细胞是否导致与年龄相关的 T 细胞免疫抑制。对脾脏和 LN 细胞的流式细胞术分析显示，老年小鼠中 CD1d 四聚体阳性 NKT 细胞的数量增加了 2 至 3 倍。为了确定来自老年小鼠的 NKT 细胞是否差异调节 T 细胞免疫，我们首先检查 NK/NKT 细胞的耗竭是否影响脾 T 细胞的增殖能力。与年轻小鼠相比，老年小鼠的完整 T 细胞制剂的增殖反应受损，而 NK/NKT 耗尽的制剂则没有。为了检查 NKT 细胞对年龄相关 T 细胞功能障碍的具体作用，在全身给予抗 CD1d mAb 的年轻小鼠和老年小鼠中检查了 Ag 特异性迟发型超敏反应和 T 细胞增殖。与年轻小鼠相比，给予对照 IgG 的老年小鼠表现出 Ag 特异性迟发型超敏反应和 T 细胞增殖受损，这可以通过全身抗 CD1d mAb 治疗来显着预防。与年龄相关的 T 细胞免疫损伤与脾细胞产生的免疫抑制性细胞因子 IL-10 的增加有关，而抗 CD1d mAb 治疗同样可以防止这种情况的发生。总之，我们的结果表明 NKT 细胞的 CD1d 激活有助于抑制老年小鼠的效应 T 细胞免疫。
NKT cells are known to regulate effector T cell immunity during tolerance, autoimmunity, and antitumor immunity. Whether age-related changes in NKT cell number or function occur remains unclear. Here, we investigated whether young vs aged (3 vs 22 mo old) mice had different numbers of CD1d-restricted NKT cells and whether activation of NKT cells by CD1d in vivo contributed to age-related suppression of T cell immunity. Flow cytometric analyses of spleen and LN cells revealed a 2- to 3-fold increase in the number of CD1d tetramer-positive NKT cells in aged mice. To determine whether NKT cells from aged mice differentially regulated T cell immunity, we first examined whether depletion of NK/NKT cells affected the proliferative capacity of splenic T cells. Compared with those from young mice, intact T cell preparations from aged mice had impaired proliferative responses whereas NK/NKT-depleted preparations did not. To examine the specific contribution of NKT cells to age-related T cell dysfunction, Ag-specific delayed-type hypersensitivity and T cell proliferation were examined in young vs aged mice given antiCD1d mAb systemically. Compared with young mice, aged mice given control IgG exhibited impaired Ag-specific delayed-type hypersensitivity and T cell proliferation, which could be significantly prevented by systemic anti-CD1d mAb treatment. The age-related impairments in T cell immunity correlated with an increase in the production of the immunosuppressive cytokine IL-10 by splenocytes that was likewise prevented by anti-CD1d mAb treatment. Together, our results suggest that CD1d activation of NKT cells contributes to suppression of effector T cell immunity in aged mice.