T cells stimulated with an analog peptide of type II collagen require the Fc receptor γ-chain to secrete interleukin-4 and suppress autoimmune arthritis in mice.
T cells stimulated with an analog peptide of type II collagen require the Fc receptor γ-chain to secrete interleukin-4 and suppress autoimmune arthritis in mice.
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DOI：
10.1002/art.30454
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发表时间：
2011-09
影响因子：
--
通讯作者：
Kang, Andrew H.
中科院分区：
文献类型：
--
作者：
Myers, Linda K.;Cullins, David L.;Brand, David D.;Kleinau, Sandra;Stuart, John M.;Kang, Andrew H.
使用胶原诱导的关节炎（CIA）模型，我们探讨了响应于II型胶原（CII）的类似肽（A9）并调节自身免疫的T细胞群的特征。A9是一种26个氨基酸的肽，类似于CII片段（CII 245-270）的序列，但在氨基酸位置260（丙氨酸替换为异亮氨酸）、261（羟脯氨酸替换为丙氨酸）和263（天冬酰胺替换为苯丙氨酸）处进行了替换。我们以前已经表明，A9深刻抑制免疫CII和CIA。为了确定抑制的机制，我们使用了转基因小鼠，其T细胞表达CII特异性受体（TCR），并进行了被动细胞转移实验。结果表明，A9对CIA的抑制依赖于T细胞。使用多参数流式细胞术，我们确定负责抑制的细胞是CD 4+，并表达高水平的FcεRIγ（FcRγ）。为了确定这一发现的意义，我们获得了FcRγ基因缺陷的小鼠进行被动转移实验。当用A9培养时，所得的FcRγ-/-CD 4 + T细胞不能转移关节炎的抑制，也不能响应于A9分泌细胞因子。总之，这些数据表明，A9引起的关节炎和Th 2细胞因子谱的抑制依赖于T细胞中FcRγ的存在。这些发现是新颖的，可能对自身免疫性关节炎患者具有治疗潜力。
Using the collagen-induced arthritis (CIA) model, we explored the characteristics of the T cell population which responds to an analog peptide (A9) of type II collagen (CII) and regulates autoimmunity. A9 is a 26 amino acid peptide analogous to the sequence of a segment of CII (CII 245-270) but with substitutions made at amino acid positions 260 (alanine for isoleucine), 261 (hydroxyproline for alanine), and 263 (asparagine for phenylalanine). We have previously shown that A9 profoundly suppresses immunity to CII and CIA. In order to determine the mechanism of suppression, we used a transgenic mouse whose T cells express a CII specific receptor (TCR) and performed passive cell transfer experiments. The results demonstrate that suppression of CIA by the A9 is dependent upon T cells. Using multiparameter flow cytometry, we determined that the cells responsible for suppression were CD4+ and expressed high levels of FcεRIγ(FcRγ). To establish the significance of this finding, we obtained mice genetically deficient in FcRγ to perform passive transfer experiments. The resulting FcRγ-/- CD4+ T cells when primed by culture with A9 could not transfer the suppression of arthritis nor secrete cytokines in response to A9. Taken together, these data suggest that the suppression of arthritis and the Th2 cytokine profile elicited by A9 is dependent upon the presence of FcRγ in the T cells. These findings are novel and may have therapeutic potential for patients with autoimmune arthritis.
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在已建立的II型胶原蛋白诱导的关节炎中，全身性白介素4治疗对软骨和骨骼破坏的保护。
DOI：
10.1186/ar14
发表时间：
1999
期刊：
Arthritis research
影响因子：
--
作者：
Joosten, L A;Lubberts, E;Helsen, M M;Saxne, T;Coenen-de Roo , C J;Heinegard, D;van den Berg , W B
通讯作者：
van den Berg , W B
影响因子：
4.4
作者：
Kim, SH;Kim, S;Robbins, PD
通讯作者：
Robbins, PD
影响因子：
8.6
作者：
Myers, LK;Tang, B;Kang, AH
通讯作者：
Kang, AH
影响因子：
4.4
作者：
Krishnan, S;Nambiar, MP;Tsokos, GC
通讯作者：
Tsokos, GC
影响因子：
1.3
作者：
Myers, Linda K.;Tang, Bo;Kang, Andrew H.
通讯作者：
Kang, Andrew H.