Conversion in vivo from an early dominant Th0/Th1 response to a Th2 phenotype during the development of collagen-induced arthritis
Conversion in vivo from an early dominant Th0/Th1 response to a Th2 phenotype during the development of collagen-induced arthritis
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DOI：
10.1002/eji.1830270623
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发表时间：
1997-06-01
影响因子：
5.4
通讯作者：
AbehsiraAmar, O
中科院分区：
文献类型：
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作者：
Doncarli, A;Stasiuk, LM;AbehsiraAmar, O
在过去的十年中，T细胞在胶原诱导关节炎（CIA）过程中的核心作用已被广泛记录。CIA的炎症特征及其在体内用Th2淋巴因子（已知可下调促炎细胞因子）治疗后的成功调节，将CIA归类为th1介导的疾病。然而，没有直接证据表明存在不同的T辅助子集。为了鉴定CIA过程中胶原特异性CD4(+) T细胞亚群的形成，在注射了Freund's完全佐剂中的牛II型胶原后，在不同时间采集易感DBA/1小鼠（H-2(q)）的淋巴结，并通过酶联免疫斑点法检测干扰素(IFN)- γ和白细胞介素(IL)-4的产生。结果清楚地表明，分泌ifn - γ、IL-4或两者同时分泌的II型胶原特异性T细胞在体内早在关节炎发病前就已发育：免疫后15天分泌ifn - γ的细胞数量已达到最大值，而在临床关节炎发病前第30天发现更多分泌IL-4的细胞。另一种策略是在体外建立胶原特异性CD4(+) T细胞系和亚系，并分析它们的淋巴因子分泌模式。免疫后8天产生的细胞系显示出Th0细胞或Th1和Th2细胞混合的淋巴因子分泌模式。在限制稀释后的第8天，60%的生长亚系是th0样（分泌ifn - γ， IL-4和IL-5）， 25%是Th1（分泌ifn - γ）。免疫后第25天，产生的亚群中33%为th0样，11%为Th1, 56%为Th2（分泌IL-4和IL-5）。此外，从55天收获的关节炎小鼠淋巴结中培养的所有亚线都分泌大量的Th2淋巴因子，14个亚线中只有3个也产生一些ifn - γ。该研究表明，在CIA过程中，胶原特异性CD4(+) T细胞反应在体内从显性Th0/Th1反应转变为明确的Th2表型。这些结果有助于我们理解在CIA诱导和临床阶段形成的胶原特异性CD4(+) T辅助亚群。
Over the past decade, the central role of T cells in the process of collagen-induced arthritis (CIA) has been extensively documented. The inflammatory features of CIA and its successful modulation after treatment in vivo with Th2 lymphokines, known to down-regulate proinflammatory cytokines, classify CIA as a Th1-mediated disease. However, no direct evidence for the presence of the different T helper subsets has been obtained. To identify the collagen-specific CD4(+) T cell subset(s) developing during the course of CIA, lymph nodes from susceptible DBA/1 mice (H-2(q)) were harvested at different times after injection of bovine type II collagen in Freund's complete adjuvant and checked by enzyme-linked immunospot assay for the production of interferon (IFN)-gamma and interleukin (IL)-4. The results clearly showed that type II collagen-specific T cells secreting either IFN-gamma, IL-4, or both, develop early in vivo, before the onset of arthritis: the number of IFN-gamma-secreting cells was already maximal 15 days after immunization, whereas more IL-4-secreting cells were found at day 30, just before the onset of clinical arthritis. Another strategy was to establish collagen-specific CD4(+) T cell lines and sublines in vitro and to analyze their lymphokine secretion pattern. Lines generated 8 days after immunization displayed a mixed lymphokine secretion pattern characteristic of Th0 cells or of a mixture of Th1 and Th2 cells. After limiting dilution of a day 8 line, 60 % of the growing sublines were Th0-like (secreting IFN-gamma, IL-4, and IL-5), and 25 % were Th1 (secreting IFN-gamma). By day 25 post-immunization, 33 % of the generated sublines were Th0-like, 11 % Th1, and 56 % Th2 (secreting IL-4 and IL-5). Moreover, all the sublines raised from the lymph nodes of arthritic mice harvested at day 55 secreted high amounts of Th2 lymphokines, and only 3 out of 14 also produced some IFN-gamma. This study demonstrates that during the course of CIA the collagen-specific CD4(+) T cell response shifts in vivo from a dominant Th0/Th1 response to a clear Th2 phenotype. These results contribute to our understanding of the collagen-specific CD4(+) T helper subsets which develop during the induction and clinical phases of CIA.