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首页> 外文期刊>Infection and immunity >CXCR6 Is a Marker for Protective Antigen-Specific Cells in the Lungs after Intranasal Immunization against Mycobacterium tuberculosis
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CXCR6 Is a Marker for Protective Antigen-Specific Cells in the Lungs after Intranasal Immunization against Mycobacterium tuberculosis

机译：CXCR6是针对结核分枝杆菌的鼻内免疫后肺中保护性抗原特异性细胞的标志物

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Convincing correlates of protective immunity against tuberculosis have been elusive. In BALB/c mice, intranasal immunization with a replication-deficient recombinant adenovirus expressing Mycobacterium tuberculosis antigen 85A (adenovirus-85A) induces protective lower respiratory tract immunity against pulmonary challenge with Mycobacterium tuberculosis, while intradermal immunization with adenovirus-85A does not. Here we report that intranasal immunization with adenovirus-85A induces expression of the chemokine receptor CXCR6 on lung CD8 T lymphocytes, which is maintained for at least 3 months. CXCR6-positive antigen-specific T cell numbers are increased among bronchoalveolar lavage-recoverable cells. Similarly, intranasal immunization with recombinant antigen 85A with adjuvant induces CXCR6 expression on lung CD4 cells in BALB/c and C57BL/6 mice, while a synthetic ESAT61–20 peptide with adjuvant induces CXCR6 expression in C57BL/6 mice. Parenteral immunization fails to do so. Upregulation of CXCR6 is accompanied by a transient elevation of serum CXCL16 after intranasal immunization, and lung cells cultured ex vivo from mice immunized intranasally show increased production of CXCL16. Administration of CXCL16 and cognate antigen intranasally to mice previously immunized parenterally increases the number of antigen-specific T lymphocytes in the bronchoalveolar lavage-recoverable population, which mediates inhibition of the early growth of Mycobacterium tuberculosis after challenge. We conclude that expression of CXCR6 on lung T lymphocytes is a correlate of local protective immunity against Mycobacterium tuberculosis after intranasal immunization and that CXCR6 and CXCL16 play an important role in the localization of T cells within lung tissue and the bronchoalveolar lavage-recoverable compartment.
机译：令人信服的针对肺结核的保护性免疫的相关性难以捉摸。在BALB / c小鼠中，用表达结核分枝杆菌抗原85A的复制缺陷型重组腺病毒进行鼻内免疫可抵抗肺结核分枝杆菌对肺部攻击的保护性下呼吸道免疫，而使用腺病毒85A进行皮内免疫则不会。在这里，我们报告说，用鼻病毒85A鼻内免疫可诱导趋化因子受体CXCR6在肺CD8 T淋巴细胞上的表达，并维持至少3个月。在支气管肺泡灌洗可恢复细胞中，CXCR6阳性抗原特异性T细胞数量增加。同样，用佐剂重组抗原85A鼻内免疫可诱导BALB / c和C57BL / 6小鼠肺CD4细胞上CXCR6表达，而具有佐剂的合成ESAT61-20肽可诱导C57BL / 6小鼠CXCR6表达。肠胃外免疫不能这样做。鼻内免疫后，CXCR6的上调伴随着血清CXCL16的短暂升高，从鼻内免疫的小鼠离体培养的肺细胞显示出CXCL16的产量增加。经事先肠胃外免疫的小鼠鼻内给予CXCL16和相关抗原会增加支气管肺泡灌洗可回收人群中抗原特异性T淋巴细胞的数量，从而介导激发后结核分枝杆菌的早期生长受到抑制。我们得出的结论是，鼻内免疫后，肺T淋巴细胞上CXCR6的表达与针对结核分枝杆菌的局部保护性免疫有关，并且CXCR6和CXCL16在T细胞在肺组织和支气管肺泡灌洗液可回收隔室中的定位中起着重要作用。

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