Multifunctional T cell reactivity with native and glycosylated type II collagen in rheumatoid arthritis.
Multifunctional T cell reactivity with native and glycosylated type II collagen in rheumatoid arthritis.
复制标题
类风湿性关节炎中多功能 T 细胞与天然和糖基化 II 型胶原的反应性。
DOI：
10.1002/art.34459
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发表时间：
2012
影响因子：
--
通讯作者：
Malmstrom,Vivianne
中科院分区：
文献类型：
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作者：
Snir,Omri;Backlund,Johan;Bostrom,Julia;Andersson,Ida;Kihlberg,Jan;Buckner,JaneH;Klareskog,Lars;Holmdahl,Rikard;Malmstrom,Vivianne
II型胶原蛋白（CII）是一种软骨特异性蛋白质，免疫耐受性的丧失可能引发自身免疫反应并导致关节炎。CII上的主要T细胞表位，氨基酸259-273，可以由几个HLA-DRB 1 *04等位基因以其天然或翻译后糖基化形式呈递。本研究进行了功能探索和比较CII-自身反应性T细胞从血液和滑液的类风湿性关节炎（RA）的患者。方法外周血获得自HLA-DRB 1 *04阳性RA患者（n = 10）和对照受试者（n = 10），并在体外刺激的CII 259 - 273表位的几个变体，即，未修饰的、在LyS-264上糖基化的、在LyS-270上糖基化的或在LyS-264和LyS-270上糖基化的。CD 154的上调用于识别响应T细胞。通过流式细胞术对白细胞介素-17（IL-17）、干扰素-γ（IFNγ）和IL-2进行细胞内染色，进一步表征这些细胞。RA患者的滑膜T细胞进行了调查parallel.ResultsMultifunctional T细胞反应对所有检查的变体的CII 259 - 273肽可以检测到RA患者，并在较小程度上，也在健康的HLA-匹配的控制（P< 0.001）。在RA患者中，血液和关节源性T细胞功能的比较显示滑膜T细胞中促炎细胞因子IFNγ水平显著升高（P= 0.027）。纵向获得的样本的研究表明，T细胞反应持续的疾病过程中，甚至包括表位spreading.ConclusionThe识别炎症T细胞反应的糖基化和nonglycosylated的主要CII表位的RA患者的变体表明，CII自身反应性RA可能是更常见的比以前认识到的。
ObjectiveType II collagen (CII) is a cartilage‐specific protein to which a loss of immune tolerance may trigger autoimmune reactions and cause arthritis. The major T cell epitope on CII, amino acids 259–273, can be presented by several HLA–DRB1*04 alleles in its native or posttranslational glycosylated form. The present study was undertaken to functionally explore and compare CII‐autoreactive T cells from blood and synovial fluid of patients with rheumatoid arthritis (RA).MethodsPeripheral blood was obtained from HLA–DRB1*04–positive RA patients (n = 10) and control subjects (n = 10) and stimulated in vitro with several variants of the CII259–273epitope, i.e., unmodified, glycosylated on Lys‐264, glycosylated on Lys‐270, or glycosylated on both Lys‐264 and Lys‐270. Up‐regulation of CD154 was used to identify responding T cells. These cells were further characterized by intracellular staining for interleukin‐17 (IL‐17), interferon‐γ (IFNγ), and IL‐2 by flow cytometry. Synovial T cells from RA patients were investigated in parallel.ResultsMultifunctional T cell responses toward all examined variants of the CII259–273peptide could be detected in RA patients and, to a lesser extent, also in healthy HLA‐matched controls (P< 0.001). In RA patients, a comparison between blood‐ and joint‐derived T cell function revealed a significant increase in levels of the proinflammatory cytokine IFNγ in synovial T cells (P= 0.027). Studies of longitudinally obtained samples showed that T cell responses were sustained over the course of disease, and even included epitope spreading.ConclusionThe identification of inflammatory T cell responses to both glycosylated and nonglycosylated variants of the major CII epitope in RA patients suggests that CII autoreactivity in RA may be more common than previously recognized.
影响因子：
--
作者：
Snir, Omri;Rieck, Mary;Gebe, John A.;Yue, Betty B.;Rawlings, Crystal A.;Nepom, Gerald;Malmstrom, Vivianne;Buckner, Jane H.
通讯作者：
Buckner, Jane H.
DOI：
10.1073/pnas.79.11.3632
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
KLARESKOG, L;FORSUM, U;WIGZELL, H
通讯作者：
WIGZELL, H
半乳糖基化羟基赖氨酸结构单元的改进合成及其在固相糖肽合成中的应用
影响因子：
2.1
作者：
B. Holm;J. Broddefalk;S. Flodell;Eric Wellner;J. Kihlberg
通讯作者：
J. Kihlberg