Treiner Emmanuel, Duban Livine, Bahram Seiamak, Radosavljevic Mirjana, Wanner Valerie, Tilloy Florence, Affaticati Pierre, Gilfillan Susan, Lantz Olivier
Laboratoire d'Immunologie and INSERM U520, Institut Curie, Paris 75005, France.
Nature. 2003 Mar 13;422(6928):164-9. doi: 10.1038/nature01433.
The evolutionary conservation of T lymphocyte subsets bearing T-cell receptors (TCRs) using invariant alpha-chains is indicative of unique functions. CD1d-restricted natural killer T (NK-T) cells that express an invariant Valpha14 TCRalpha chain have been implicated in microbial and tumour responses, as well as in auto-immunity. Here we show that T cells that express the canonical hValpha7.2-Jalpha33 or mValpha19-Jalpha33 TCR rearrangement are preferentially located in the gut lamina propria of humans and mice, respectively, and are therefore genuine mucosal-associated invariant T (MAIT) cells. Selection and/or expansion of this population requires B lymphocytes, as MAIT cells are absent in B-cell-deficient patients and mice. In addition, we show that MAIT cells are selected and/or restricted by MR1, a monomorphic major histocompatibility complex class I-related molecule that is markedly conserved in diverse mammalian species. MAIT cells are not present in germ-free mice, indicating that commensal flora is required for their expansion in the gut lamina propria. This indicates that MAIT cells are probably involved in the host response at the site of pathogen entry, and may regulate intestinal B-cell activity.
使用恒定α链的带有T细胞受体（TCR）的T淋巴细胞亚群的进化保守性表明其具有独特功能。表达恒定Valpha14 TCRα链的CD1d限制性自然杀伤T（NK-T）细胞已被证明参与微生物和肿瘤反应以及自身免疫。在此我们表明，表达典型的人Valpha7.2-Jalpha33或小鼠Valpha19-Jalpha33 TCR重排的T细胞分别优先定位于人和小鼠的肠道固有层，因此是真正的黏膜相关恒定T（MAIT）细胞。该细胞群体的选择和/或扩增需要B淋巴细胞，因为在B细胞缺陷的患者和小鼠中不存在MAIT细胞。此外，我们表明MAIT细胞由MR1选择和/或限制，MR1是一种单态性主要组织相容性复合体I类相关分子，在不同哺乳动物物种中显著保守。无菌小鼠中不存在MAIT细胞，这表明共生菌群是其在肠道固有层中扩增所必需的。这表明MAIT细胞可能参与病原体进入部位的宿主反应，并可能调节肠道B细胞活性。
