The degree of CD4+ T cell autoreactivity determines cellular pathways underlying inflammatory arthritis.
The degree of CD4+ T cell autoreactivity determines cellular pathways underlying inflammatory arthritis.
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CD4+ T 细胞自身反应的程度决定了炎症性关节炎的细胞通路。
DOI：
10.4049/jimmunol.1302528
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发表时间：
2014-04-01
期刊：
影响因子：
--
通讯作者：
Caton AJ
中科院分区：
文献类型：
--
作者：
Perng OA;Aitken M;Rankin AL;Garcia V;Kropf E;Erikson J;Garlick DS;Caton AJ
尽管已经发现针对不同细胞途径的疗法（例如抗细胞因子与抗B细胞疗法）对于至少一些患有炎性关节炎的患者是有效的策略，但是确定哪些途径促进关节炎发展的机制知之甚少。我们使用转基因小鼠模型来研究CD 4 + T细胞对替代自身肽反应的变化如何影响关节炎发展所需的细胞途径。与自身肽高度反应的CD 4 + T细胞会诱导炎症性关节炎，对雄性和雌性小鼠的影响相同。关节炎通过B细胞非依赖性机制发展，尽管它可以通过抗TNF治疗来抑制，该治疗防止了效应CD 4 + Th 17细胞在治疗小鼠的关节中的积累。相比之下，关节炎在自身反应性较弱的CD 4 + T细胞应答的背景下以显著的女性偏好发展，并且B细胞在疾病发病机制中发挥突出作用。在这种较低的CD 4 + T细胞自身反应性的情况下，B细胞促进自身反应性CD 4+效应T细胞（包括Th 17细胞）的形成，并且IL-17是关节炎发展所需的。这些研究表明，CD 4 + T细胞对自身肽的反应性程度可以在确定是否可以靶向不同的细胞途径以预防炎性关节炎的发展方面发挥重要作用。
Although therapies targeting distinct cellular pathways (e.g. anti-cytokine versus anti-B cell therapy) have been found to be an effective strategy for at least some patients with inflammatory arthritis, the mechanisms that determine which pathways promote arthritis development are poorly understood. We have used a transgenic mouse model to examine how variations in the CD4+ T cell response to a surrogate self-peptide can affect the cellular pathways that are required for arthritis development. CD4+ T cells that are highly reactive with the self-peptide induce inflammatory arthritis that affects male and female mice equally. Arthritis develops by a B cell-independent mechanism, although it can be suppressed by an anti-TNF treatment, which prevented the accumulation of effector CD4+ Th17 cells in the joints of treated mice. By contrast, arthritis develops with a significant female bias in the context of a more weakly autoreactive CD4+ T cell response, and B cells play a prominent role in disease pathogenesis. In this setting of lower CD4+ T cell autoreactivity, B cells promote the formation of autoreactive CD4+ effector T cells (including Th17 cells), and IL-17 is required for arthritis development. These studies show that the degree of CD4+ T cell reactivity for a self-peptide can play a prominent role in determining whether distinct cellular pathways can be targeted to prevent the development of inflammatory arthritis.
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DOI：
10.1007/s00281-003-0125-3
发表时间：
2003-08-01
期刊：
SPRINGER SEMINARS IN IMMUNOPATHOLOGY
影响因子：
--
作者：
Li, P;Schwarz, EM
通讯作者：
Schwarz, EM
影响因子：
--
作者：
Cohen, Stanley B.;Emery, Paul;Totoritis, Mark C.
通讯作者：
Totoritis, Mark C.
影响因子：
158.5
作者：
Edwards, JCW;Szczepanski, L;Shaw, T
通讯作者：
Shaw, T
影响因子：
--
作者：
Hueber, W;Kidd, BA;Robinson, WH
通讯作者：
Robinson, WH
DOI：
10.1084/jem.189.10.1639
发表时间：
1999-05-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chan OT;Hannum LG;Haberman AM;Madaio MP;Shlomchik MJ
通讯作者：
Shlomchik MJ