T Cells Specific for a Mycobacterial Glycolipid Expand after Intravenous Bacillus Calmette-Guérin Vaccination.
T Cells Specific for a Mycobacterial Glycolipid Expand after Intravenous Bacillus Calmette-Guérin Vaccination.
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DOI：
10.4049/jimmunol.2001065
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发表时间：
2021-03-15
期刊：
影响因子：
--
通讯作者：
Seshadri C
中科院分区：
文献类型：
--
作者：
Layton ED;Barman S;Wilburn DB;Yu KKQ;Smith MT;Altman JD;Scriba TJ;Tahiri N;Minnaard AJ;Roederer M;Seder RA;Darrah PA;Seshadri C
皮内接种牛分枝杆菌卡介苗（BCG）可保护婴儿免受播散性结核病的侵害，静脉接种BCG可保护非人灵长类动物（NHP）免受肺结核和肺外结核的侵害。在人类和NHP中，保护被认为是由T细胞介导的，T细胞通常识别与主要组织相容性复合体蛋白结合的细菌肽抗原。然而，在脊椎动物进化过程中，T细胞获得了识别与抗原呈递细胞上表达的CD1a、CD1b和CD1c蛋白结合的脂质抗原的能力。目前尚不清楚卡介苗是否诱导T细胞对分枝杆菌脂质的免疫，以及CD1限制性T细胞是否驻留在肺中。在这里，我们开发并验证了猕猴（Mamu）CD1b和CD1c四聚体，以探测特异性葡萄糖单霉菌酸盐（GMM），免疫显性分枝杆菌脂质抗原的T细胞的体外表型和功能。我们发现，CD1b和CD1c将GMM呈递给人类和NHP中的T细胞。我们发现，GMM特异性T细胞在静脉注射BCG后四周在恒河猴血液中扩增，这已被证明可以保护NHP，在结核分枝杆菌挑战后具有接近灭菌的功效。接种疫苗后，这些T细胞在支气管肺泡液中以高频率检测到，并表达与驻留记忆T细胞相关的标记物CD69和CD103。因此，我们的数据扩展了已知由全细胞分枝杆菌疫苗（如BCG）诱导的T细胞库，并表明脂质抗原特异性T细胞驻留在肺部，它们可能有助于保护性免疫。
Intradermal vaccination with Mycobacterium bovis bacille Calmette-Guerin (BCG) protects infants from disseminated tuberculosis, and intravenous BCG protects non-human primates (NHP) against pulmonary and extrapulmonary tuberculosis. In humans and NHP, protection is thought to be mediated by T-cells, which typically recognize bacterial peptide antigens bound to major histocompatibility complex proteins. However, during vertebrate evolution, T cells acquired the capacity to recognize lipid antigens bound to CD1a, CD1b, and CD1c proteins expressed on antigen-presenting cells. It is unknown whether BCG induces T cell immunity to mycobacterial lipids and if CD1-restricted T cells are resident in the lung. Here, we developed and validated Macaca mulatta (Mamu) CD1b and CD1c tetramers to probe ex vivo phenotypes and functions of T cells specific for glucose monomycolate (GMM), an immunodominant mycobacterial lipid antigen. We discovered that CD1b and CD1c present GMM to T cells in both humans and NHP. We show that GMM-specific T cells are expanded in rhesus macaque blood four weeks after intravenous BCG, which has been shown to protect NHP with near-sterilizing efficacy upon Mycobacterium tuberculosis challenge. After vaccination, these T cells are detected at high frequency within bronchoalveolar fluid and express CD69 and CD103, markers associated with resident memory T cells. Thus, our data expand the repertoire of T cells known to be induced by whole cell mycobacterial vaccines like BCG and show that lipid antigen-specific T cells are resident in the lungs where they may contribute to protective immunity.
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作者：
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通讯作者：
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影响因子：
--
作者：
Layre E;Sweet L;Hong S;Madigan CA;Desjardins D;Young DC;Cheng TY;Annand JW;Kim K;Shamputa IC;McConnell MJ;Debono CA;Behar SM;Minnaard AJ;Murray M;Barry CE 3rd;Matsunaga I;Moody DB
通讯作者：
Moody DB