Russano Anna M, Agea Elisabetta, Corazzi Lanfranco, Postle Antyony D, De Libero Gennaro, Porcelli Steven, de Benedictis Fernando M, Spinozzi Fabrizio
Experimental Immunology and Allergy, Department of Clinical and Experimental Medicine, University of Perugia, Italy.
J Allergy Clin Immunol. 2006 May;117(5):1178-84. doi: 10.1016/j.jaci.2006.01.001. Epub 2006 Feb 21.
Evidences from mice and human beings indicate that gammadelta T cells could be relevant in recognition of stress-induced self and/or yet unidentified inhaled foreign antigens. Their specificity differs from classic MHC-restricted alphabeta T cells and involves the immunoglobulin-like structure of the gammadelta T-cell receptor with the recognition of small organic molecules, alkylamines, and self lipid compounds presented by CD1+ dendritic cells.
Because CD1 receptors are mainly devoted to lipid antigen presentation, we sought to determine whether exogenous pollen membrane lipids may act as allergens for CD1-restricted gammadelta T cells.
Peripheral blood and nasal mucosa-associated gammadelta T cells were cloned from normal controls and cypress-sensitive subjects and tested for their antigen specificity and CD1-restriction with phospholipids extracted from tree pollen grains, as well with other natural or synthetic compounds. Phospholipid reactivity of cloned gammadelta T cells was measured by mean of proliferative response and cytokine release as well as by testing their helper activity on IgE production in vitro and in vivo.
Cloned gammadelta T lymphocytes from subjects with allergy, but not normal controls, were found to recognize pollen-derived phosphatidyl-ethanolamine (PE) in a CD1d-restricted fashion. Only 16:0/18:2 and 18:2/18:2 PE were stimulatory, whereas no response was recorded for disaturated PE, phosphatidylcholine, neutral lipids, or protein extract. Proliferating clones secreted both T(H)1-type and T(H)2-type cytokines and drove IgE production in vitro and in vivo.
CD1d-restricted gammadelta T cells specific for phospholipids can represent a key mucosal regulatory subset for the control of early host reactivity against tree pollens.
By knowing how lipid allergen constituents interact with mucosal immune system, we can expand our possibilities in diagnostic and therapeutic interventions.
来自小鼠和人类的证据表明，γδT细胞可能与应激诱导的自身抗原和/或尚未明确的吸入性外来抗原的识别有关。它们的特异性不同于经典的MHC限制性αβT细胞，涉及γδT细胞受体的免疫球蛋白样结构，可识别由CD1+树突状细胞呈递的小分子有机化合物、烷基胺和自身脂质化合物。
由于CD1受体主要负责脂质抗原呈递，我们试图确定外源性花粉膜脂质是否可作为CD1限制性γδT细胞的变应原。
从正常对照和对柏树敏感的受试者中克隆外周血和鼻黏膜相关γδT细胞，并用从花粉粒中提取的磷脂以及其他天然或合成化合物检测其抗原特异性和CD1限制性。通过增殖反应、细胞因子释放以及检测其在体外和体内对IgE产生的辅助活性来测量克隆的γδT细胞的磷脂反应性。
发现来自过敏受试者而非正常对照的克隆γδT淋巴细胞以CD1d限制性方式识别花粉衍生的磷脂酰乙醇胺（PE）。只有16:0/18:2和18:2/18:2 PE具有刺激作用，而对于二饱和PE、磷脂酰胆碱、中性脂质或蛋白质提取物未记录到反应。增殖克隆分泌T(H)1型和T(H)型细胞因子，并在体外和体内驱动IgE产生。
对磷脂具有特异性的CD1d限制性γδT细胞可能是控制宿主对树花粉早期反应性的关键黏膜调节亚群。
通过了解脂质变应原成分如何与黏膜免疫系统相互作用，我们可以扩大诊断和治疗干预的可能性。
