Do Jeongsu, Visperas Anabelle, Freeman Michael L, Jang Eunjung, Kim Sohee, Malissen Bernard, Min Booki
Department of Immunology, Lerner Research Institute, Lerner Research InstituteCleveland Clinic Foundation, Cleveland, OH, USA.
Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Case 906, Institut National de la Santé et de la Recherche Médicale, U631, Centre National de la Recherche Scientifique, UMR6102, Marseille, France.
Eur J Immunol. 2016 Feb;46(2):340-6. doi: 10.1002/eji.201545919. Epub 2015 Dec 7.
T cells expressing the γδ TCR are dominant T-cell subsets in the intestinal immune system. We previously demonstrated that γδ T cells play important roles in augmenting Th17-type colitogenic immune responses in a T-cell-induced colitic inflammation model. However, its underlying mechanism remains poorly understood. In this study, an in vitro coculture system using effector T cells enriched in gut Ag-reactive cells was employed as a readout tool to search for gut Ag presenting APCs. We found that the presence of γδ T cells dramatically enhances gut Ag presentation within the mLN in mice. Gut Ag presentation by CD11b(+) DC subsets was particularly controlled by γδ T cells. Interestingly, γδ T-cell entry to the lymph nodes was essential to improve the Ag presentation. Therefore, our results highlight that γδ T cells play a previously unrecognized role to support colitogenic immunity by regulating gut Ag presentation in the draining LN.
表达γδTCR的T细胞是肠道免疫系统中占主导地位的T细胞亚群。我们之前证明,在T细胞诱导的结肠炎炎症模型中,γδT细胞在增强Th17型促结肠炎免疫反应中发挥重要作用。然而,其潜在机制仍知之甚少。在本研究中,使用富含肠道抗原反应性细胞的效应T细胞的体外共培养系统作为读出工具,以寻找肠道抗原呈递抗原递呈细胞(APC)。我们发现,γδT细胞的存在显著增强了小鼠肠系膜淋巴结(mLN)内的肠道抗原呈递。CD11b(+)树突状细胞亚群的肠道抗原呈递尤其受γδT细胞的调控。有趣的是,γδT细胞进入淋巴结对于改善抗原呈递至关重要。因此,我们的结果突出表明,γδT细胞通过调节引流淋巴结中的肠道抗原呈递,在支持促结肠炎免疫方面发挥了以前未被认识到的作用。