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莱姆关节炎滑膜γδ T细胞对伯氏疏螺旋体脂蛋白和脂化六肽有反应。

Lyme arthritis synovial gamma delta T cells respond to Borrelia burgdorferi lipoproteins and lipidated hexapeptides.

作者信息

Vincent M S, Roessner K, Sellati T, Huston C D, Sigal L H, Behar S M, Radolf J D, Budd R C

机构信息

Department of Medicine, University of Vermont College of Medicine, Burlington 05405-0068, USA.

出版信息

J Immunol. 1998 Nov 15;161(10):5762-71.

PMID:9820558
Abstract

Lyme arthritis synovial fluid contains a large proportion of gamma delta T cells that proliferates upon stimulation with the causative spirochete, Borrelia burgdorferi. A panel of Borrelia-reactive gamma delta T cell clones was derived from synovial fluid of two patients with Lyme arthritis. Each of six gamma delta clones from one patient used the V delta 1 TCR segment but had otherwise unique CDR3 sequences and diverse V gamma segment usage. Stimulation of the V delta 1 clones was optimal in the presence of Borrelia, dendritic cells, and exogenous IL-2, which was reflected by proliferation, TCR down-modulation, as well as induction of CD25 and Fas ligand expression. Stimulation by B. burgdorferi-pulsed dendritic cells withstood chemical fixation and was not restricted to class I or class II MHC, CD1a, CD1b, or CD1c. In contrast, anti-gamma delta antibody potently inhibited proliferation. Extraction of B. burgdorferi lipoproteins with Triton X-114 enriched for the stimulatory component. This was confirmed using lipidated vs nonlipidated hexapeptides of Borrelia outer surface proteins. These observations suggest that synovial V delta 1 T cells may mediate an innate immune response to common lipoprotein products of spirochetes.

摘要

莱姆关节炎滑液含有大量的γδ T细胞,这些细胞在受到致病螺旋体——伯氏疏螺旋体刺激后会增殖。一组对伯氏疏螺旋体有反应的γδ T细胞克隆源自两名莱姆关节炎患者的滑液。来自一名患者的六个γδ克隆中的每一个都使用Vδ1 TCR片段,但具有独特的CDR3序列和多样的Vγ片段使用情况。在存在伯氏疏螺旋体、树突状细胞和外源性白细胞介素-2的情况下,Vδ1克隆的刺激最为理想,这通过增殖、TCR下调以及CD25和Fas配体表达的诱导得以体现。经伯氏疏螺旋体脉冲处理的树突状细胞的刺激能耐受化学固定,且不限于I类或II类主要组织相容性复合体、CD1a、CD1b或CD1c。相比之下,抗γδ抗体能有效抑制增殖。用Triton X-114提取伯氏疏螺旋体脂蛋白可富集刺激成分。使用伯氏疏螺旋体外膜蛋白的脂化与非脂化六肽证实了这一点。这些观察结果表明,滑膜Vδ1 T细胞可能介导对螺旋体常见脂蛋白产物的固有免疫反应。

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