Peripheral blood responses to specific antigens and CD28 in sarcoidosis
Peripheral blood responses to specific antigens and CD28 in sarcoidosis
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DOI：
10.1016/j.rmed.2012.01.012
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发表时间：
2012-05-01
影响因子：
4.3
通讯作者：
Thomas, Paul S.
中科院分区：
文献类型：
--
作者：
Ahmadzai, Hasib;Cameron, Barbara;Thomas, Paul S.
背景：诱发结节病炎症的潜在抗原包括分枝杆菌抗原和自身抗原。偶然的是，也会发生对常见回忆抗原的外周无反应性，这可能是由于受损的树突细胞或调节性T细胞应答，或受损的T细胞共刺激。方法：检测16例结节病患者（n = 16）和22例健康对照者（n = 22）外周血单个核细胞（PBMC）对候选抗原的反应，用抗CD 3/CD 28包被的磁珠刺激PBMC;结核分枝杆菌ESAT-6和KatG肽;波形蛋白和赖氨酰tRNA肽;和常见的回忆抗原，包括巨细胞病毒（CMV）细胞裂解物以及CMV、EB病毒、流感病毒（CEF）肽。与纯化蛋白衍生物（PPD）阴性健康对照受试者相比，结节病中ESAT-6/KatG肽刺激诱导更多数量的产生IFN-γ的T细胞，并升高IL-2、IL-6和TNF-α的产生。来自结节病患者的PBMC显示在用CMV裂解物、CEF肽和CD 3/CD 28珠刺激后产生IFN-γ的T细胞减少;并且在CD 3/CD 28活化后IL-4和TNF-α产生减少。结核抗原相比PPD阴性对照，但减少了T细胞对常见回忆抗原的应答。一种起作用的机制可能是T细胞CD 28共刺激的损害。皇冠版权所有（C）2012由爱思唯尔有限公司出版。保留所有权利。
Background: Potential antigens inducing sarcoid inflammation include mycobacterial and autoantigens. Paradoxically, peripheral anergy to common recall antigens also occurs, possibly due to impaired dendritic cell or regulatory T-cell responses, or impaired T-cell co-stimulation. The purpose of this study was to compare peripheral blood responses of patients with sarcoidosis to candidate antigens, and examine CD28 T-cell co-stimulation.Methods: Peripheral blood mononuclear cell (PBMC) responses were examined from patients with sarcoidosis (n = 16) and healthy control subjects (n = 22) following PBMC stimulation with: anti-CD3/CD28 coated beads; Mycobacterium tuberculosis ESAT-6 and KatG peptides; vimentin and lysyl tRNA peptides; and common recall antigens, including cytomegalovirus (CMV) cell lysate as well as CMV, Epstein-Barr virus, influenza virus (CEF) peptides.Results: ESAT-6/KatG peptide stimulation induced greater numbers of IFN-gamma producing T-cells, and elevated IL-2, IL-6 and TNF-alpha production in sarcoidosis compared to purified protein derivative (PPD)-negative healthy control subjects. PBMCs from patients with sarcoidosis showed reduced IFN-gamma producing T-cells following stimulation with CMV lysate, CEF peptides and CD3/CD28 beads; and reduced IL-4 and TNF-alpha production following CD3/CD28 activation.Conclusions: Patients with sarcoidosis exhibit greater PBMC responses to M. tuberculosis antigens compared to PPD-negative controls, but reduced T-cell responses to common recall antigens. One contributing mechanism may be impairment of T-cell CD28 co-stimulation. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.