Suppression of murine collagen-induced arthritis with monoclonal anti-Ia antibodies and augmentation with IFN-gamma.

Suppression of murine collagen-induced arthritis with monoclonal anti-Ia antibodies and augmentation with IFN-gamma.
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DOI:
10.4049/jimmunol.141.6.1958
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发表时间:
1988-09
影响因子:
4.4
通讯作者:
Sheldon M. Cooper;Subramaniam Sriram;G. Ranges
Sheldon M. Cooper;Subramaniam Sriram;G. Ranges
中科院分区:
医学2区
文献类型:
--
作者:
Sheldon M. Cooper;Subramaniam Sriram;G. Ranges

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胶原诱导的关节炎(CIA)是一种实验模型,其中对II型胶原(CII)的特异性免疫应答与炎性关节炎的发展相关。在这项研究中,我们评估了早期和延迟治疗抗Ia单克隆抗体和IFN-γ对小鼠CIA的影响。CII免疫接种时给予抗Ia单克隆抗体可降低关节炎的发病率并延迟关节炎的发作,而免疫接种后2周开始的抗Ia治疗对关节炎的发病率或发作均无影响。两种治疗方案均未导致抗体滴度或对CII的增殖反应显著降低。由于IFN-γ增加Ia在多种细胞中的表达,我们确定了其对关节炎发病率和发作的影响。当IFN-γ治疗在免疫时开始时,关节炎的发病率增加,并且关节炎发作更快。用IFN-γ治疗没有导致抗CII抗体水平的增加。这些结果支持Ia表达在诱导鼠胶原诱导性关节炎中的重要性,并表明抗Ia抗体的抑制和IFN-γ的增强不是对CII的体液反应变化的结果,但可能是由于靶器官内的局部作用。
Collagen-induced arthritis (CIA) is an experimental model in which a specific immune response to type II collagen (CII) is associated with the development of inflammatory arthritis. In this study, we evaluated the effects of early and delayed treatments with anti-Ia mAb and IFN-gamma on murine CIA. Administration of anti-Ia mAb at the time of immunization with CII decreased the incidence and delayed the onset of arthritis, whereas anti-Ia treatments begun 2 wk after immunization had no effect upon either arthritis incidence or onset. Neither treatment protocol resulted in a significant decrease in antibody titer or proliferative response to CII. Because IFN-gamma increases Ia expression in a variety of cells, we determined its effect on arthritis incidence and onset. When IFN-gamma treatments were begun at the time of immunization the incidence of arthritis was increased and arthritis onset was more rapid. Treatment with IFN-gamma did not result in an increase in anti-CII antibody levels. These results support the importance of Ia expression in the induction of murine collagen-induced arthritis, and suggest that suppression with anti-Ia antibodies and augmentation with IFN-gamma are not the result of changes in the humoral response to CII, but may be due to local effects within the target organ.