IL-17-Producing Innate and Pathogen-Specific Tissue Resident Memory γδ T Cells Expand in the Lungs of Bordetella pertussis-Infected Mice
IL-17-Producing Innate and Pathogen-Specific Tissue Resident Memory γδ T Cells Expand in the Lungs of Bordetella pertussis-Infected Mice
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DOI：
10.4049/jimmunol.1601024
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发表时间：
2017-01-01
影响因子：
4.4
通讯作者：
Mills, Kingston H. G.
中科院分区：
文献类型：
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作者：
Misiak, Alicja;Wilk, Mieszko M.;Mills, Kingston H. G.
γδT 细胞在粘膜表面感染的保护性免疫中发挥作用，而且还通过先天产生 IL-17 介导某些自身免疫性疾病的病理。最近的报告表明，gd T 细胞可以具有与传统 ab T 细胞类似的记忆。在这项研究中，我们研究了 gd T 细胞在对呼吸道病原体百日咳博德特氏菌的免疫中的作用。 gd T 细胞（主要是 V delta 4-gamma 1(-) 细胞）早在感染后 2 小时就在肺部产生 IL-17。在缺乏早期 IL-17 的情况下，原发感染期间的细菌负荷显着增强，抗菌肽的诱导减少。攻击后 7-14 天，在肺部检测到第二个 γ δ T 细胞峰值，这些 γ δ T 细胞具有病原体特异性。在 APC 存在的情况下，来自受感染小鼠（而非幼稚小鼠）肺部的 γ δ T 细胞（仅是 V γ 4）会产生 IL-17，以响应热灭活的百日咳博德特氏菌。此外，来自再次感染百日咳博德特氏菌的小鼠肺部的 gd T 细胞比来自受感染的未免疫小鼠的 γ δ T 细胞产生显着更多的 IL-17。具有组织驻留记忆T细胞表型（CD69（+）CD103（+））的γδT细胞在百日咳博德特氏菌感染期间在肺部扩增，并在恢复期小鼠再次感染后迅速增殖。我们的研究结果表明，肺 γ δ T 细胞提供了先天 IL-17 的早期来源，可促进抗菌肽的产生，而病原体特异性 V γ 4 细胞则在针对百日咳博德特氏菌的适应性免疫记忆中发挥作用。
gamma delta T cells play a role in protective immunity to infection at mucosal surface, but also mediate pathology in certain autoimmune diseases through innate IL-17 production. Recent reports have suggested that gd T cells can have memory analogous to conventional ab T cells. In this study we have examined the role of gd T cells in immunity to the respiratory pathogen Bordetella pertussis. gd T cells, predominantly V delta 4-gamma 1(-) cells, produced IL-17 in the lungs as early as 2 h after infection. The bacterial burden during primary infection was significantly enhanced and the induction of antimicrobial peptides was reduced in the absence of early IL-17. A second peak of gamma delta T cells is detected in the lungs 7-14 d after challenge and these gamma delta T cells were pathogen specific. gamma delta T cells, exclusively V gamma 4, from the lungs of infected but not naive mice produced IL-17 in response to heatkilled B. pertussis in the presence of APC. Furthermore, gd T cells from the lungs of mice reinfected with B. pertussis produced significantly more IL-17 than gamma delta T cells from infected unprimed mice. gamma delta T cells with a tissue resident memory T cell phenotype (CD69(+) CD103(+)) were expanded in the lungs during infection with B. pertussis and proliferated rapidly after rechallenge of convalescent mice. Our findings demonstrate that lung gamma delta T cells provide an early source of innate IL-17, which promotes antimicrobial peptide production, whereas pathogen-specific V gamma 4 cells function in adaptive immunological memory against B. pertussis.