Tracking of Proinflammatory Collagen-Specific T Cells in Early and Late Collagen-Induced Arthritis in Humanized Mice1
Tracking of Proinflammatory Collagen-Specific T Cells in Early and Late Collagen-Induced Arthritis in Humanized Mice1
复制标题
追踪人源化小鼠早期和晚期胶原诱导关节炎中的促炎胶原特异性 T 细胞1
作者：
P. Svendsen;C. Andersen;N. Willcox;A. Coyle;R. Holmdahl;T. Kamradt;L. Fugger
类风湿性关节炎是一种与某些HLA-DR4亚型相关的慢性炎症性疾病。目标自身抗原(s)是未知的，但II型胶原（CII）是一个候选，具有单一免疫显性dr4限制性261-273 T细胞表位（CII(261-273)）。在本研究中，我们制备了HLA-DR4:CII（261-273）四聚体，并分析了dr4转基因小鼠早期和晚期胶原诱导关节炎的外周血、淋巴结和滑液细胞，以更全面地了解CII反应性Th细胞在疾病发展中的作用。在刺激后1-2周的血液中，它们的频率增加了20倍，在急性关节炎关节中甚至更多。我们的数据强烈表明，cii特异性的Th细胞对于胶原诱导的关节炎是必要的，但不是充分的。cii特异性Th细胞表现出活化的促炎Th1表型，其扩增与关节炎的发病和严重程度以及抗cii抗体水平相关。令人惊讶的是，在关节炎的第一个临床症状出现后不久，活化的HLA-DR4:CII四聚体+细胞在滑液中检测不到，在血液中也很少见，但在淋巴结中却持续存在。因此，未来的人体研究应将重点放在早期关节炎患者及其滑膜细胞上，以重新评估类风湿关节炎中cii特异性或其他Th细胞的发生和致病重要性。
Rheumatoid arthritis is a chronic inflammatory disease associated with certain HLA-DR4 subtypes. The target autoantigen(s) is unknown, but type II collagen (CII) is a candidate, with a single immunodominant DR4-restricted 261–273 T cell epitope (CII(261–273)). In the present study, we have prepared HLA-DR4:CII(261–273) tetramers and analyzed peripheral blood, lymph node, and synovial fluid cells from DR4-transgenic mice with early and late collagen-induced arthritis to draw a fuller picture of the role of CII-reactive Th cells in disease development. Their frequencies increased ∼20-fold in blood 1–2 wk postimmunization, and even more in acutely arthritic joints. Our data strongly suggest that CII-specific Th cells are necessary, but not sufficient for collagen-induced arthritis. The CII-specific Th cells displayed an activated proinflammatory Th1 phenotype, and their expansion correlated with onset and severity of arthritis and also with anti-CII Ab levels. Surprisingly, shortly after the first clinical signs of arthritis, activated HLA-DR4:CII tetramer+ cells became undetectable in the synovial fluid and rare in the blood, but persisted in lymph nodes. Consequently, future human studies should focus on patients with early arthritis, and on their synovial cells, to re-evaluate the occurrence and pathogenic importance of CII-specific or other Th cells in rheumatoid arthritis.
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由单个肽结合的 II 类 MHC 蛋白的细胞表面表达。
DOI：
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发表时间：
1995
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Ignatowicz,L;Winslow,G;Bill,J;Kappler,J;Marrack,P
通讯作者：
Marrack,P
影响因子：
56.9
作者：
TRENTHAM, DE;DYNESIUSTRENTHAM, RA;WEINER, HL
通讯作者：
WEINER, HL
影响因子：
4.4
作者：
K. Terato;K. Hasty;R. Reife;M. Cremer;A. Kang;J. Stuart
通讯作者：
K. Terato;K. Hasty;R. Reife;M. Cremer;A. Kang;J. Stuart
影响因子：
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作者：
CUSH, JJ;LIPSKY, PE
通讯作者：
LIPSKY, PE