CD1-restricted recognition of exogenous and self-lipid antigens by duodenal γδ plus T lymphocytes
CD1-restricted recognition of exogenous and self-lipid antigens by duodenal γδ plus T lymphocytes
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DOI：
10.4049/jimmunol.178.6.3620
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发表时间：
2007-03-15
影响因子：
4.4
通讯作者：
Spinozzi, Fabrizio
中科院分区：
文献类型：
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作者：
Russano, Anna M.;Bassotti, Gabrio;Spinozzi, Fabrizio
γ δ T细胞存在于肠粘膜上皮和分泌维持组织完整性所必需的因子。这些细胞识别的Ags定义不明确，尽管在小鼠中涉及非经典MHC I类分子。由于MHC i类CD1受体在上皮细胞和树突状肠细胞表面广泛表达，并具有向T细胞呈递脂质Ags的能力，我们假设这些分子可能向肠γ δ T淋巴细胞呈递自体和/或外源磷脂。克隆正常人十二指肠粘膜活检的上皮内T淋巴细胞，并使用CD1a-、CD1b-、CD1c-或cd1d转染的C1R淋巴母细胞样细胞或HeLa细胞系作为apc暴露于天然和合成磷脂中。研究了它们的细胞溶解特性和调节细胞因子的分泌。从十二指肠粘膜获得的大部分克隆（高达70%）是TCR α β (+), CD4（+）或CD8(+)，而20%是CD4(-)CD8(-)（6个克隆）或TCR γ δ(+)（12个克隆）。通过[H-3]胸腺嘧啶掺入和IL-4释放试验测量，相关百分比（高达66%）的TCR γ - δ(+)但很少（< 5%）的TCR α - β (+) T细胞克隆对CD1分子呈现的合成和/或天然磷脂有反应。在大多数磷脂特异性γ δ T细胞克隆中观察到th1样细胞溶解和功能活性以及分泌调节细胞因子的能力。因此，来自人十二指肠黏膜的大量TCR γ δ(+)和少数TCR α β(+)以cd1受限的方式识别外源性磷脂。这种适应性反应可能有助于粘膜稳态，但也可能有利于炎症性或过敏性肠道疾病的出现。
gamma delta T cells are present in the mucosal intestinal epithelia and secrete factors necessary to maintain tissue integrity. Ags recognized by these cells are poorly defined, although in mice non-classical MHC class I molecules have been implicated. Since MHC class I-like CD1 receptors are widely expressed at the surface of epithelial and dendritic intestinal cells and have the capacity to present lipid Ags to T cells, we hypothesized that these molecules might present autologous and/or exogenous phospholipids to intestinal gamma delta T lymphocytes. Intraepithelial T lymphocytes from normal human duodenal mucosal biopsies were cloned and exposed to natural and synthetic phospholipids using CD1a-, CD1b-, CD1c- or CD1d-transfected C1R lymphoblastoid or HeLa cell lines as APCs. Their cytolytic properties and regulatory cytokine secretion were also examined. Most clones obtained from duodenal mucosa (up to 70%) were TCR alpha beta(+), and either CD4(+) or CD8(+), whereas 20% were CD4(-)CD8(-) (6 clones) or TCR gamma delta(+) (12 clones). A relevant percentage (up to 66%) of TCR gamma delta(+) but few (< 5%) TCR alpha beta(+) T cell clones responded to synthetic and/or natural phospholipids presented by CD1 molecules, as measured by both [H-3]thymidine incorporation and IL-4 release assays. A Th1-like cytolytic and functional activity along with the ability to secrete regulatory cytokines was observed in most phospholipid-specific gamma delta T cell clones. Thus, a substantial percentage of TCR gamma delta(+) but few TCR alpha beta(+) from human duodenal mucosa recognize exogenous phospholipids in a CD1-restricted fashion. This adaptive response could contribute to mucosal homeostasis, but could also favor the emergence of inflammatory or allergic intestinal diseases.