B cell depletion enhances T regulatory cell activity essential in the suppression of arthritis.
B cell depletion enhances T regulatory cell activity essential in the suppression of arthritis.
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DOI：
10.4049/jimmunol.1101844
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发表时间：
2011-11-01
期刊：
影响因子：
--
通讯作者：
Finnegan A
中科院分区：
文献类型：
--
作者：
Hamel KM;Cao Y;Ashaye S;Wang Y;Dunn R;Kehry MR;Glant TT;Finnegan A
B细胞耗竭治疗类风湿性关节炎（RA）的疗效已引起人们对其机制的兴趣。由于RA自身抗体的减少与临床结果不一定相关，其他机制可能是有效的。我们之前报道过在蛋白多糖诱导的关节炎（PGIA）中，B细胞消耗抑制自身反应性T细胞反应。最近对B细胞耗竭治疗的研究也表明B细胞在抑制调节机制中的作用。本研究表明，B细胞抑制PGIA中T调节细胞（Treg）的扩增和功能。利用抗cd20单抗，我们从PGIA小鼠中去除B细胞，并评估Treg细胞群。与对照抗体处理小鼠相比，B细胞缺失小鼠的Treg细胞百分比升高，CD4+ T细胞表达Foxp3和CD25的比例更高。在每个细胞的基础上，来自B细胞缺失小鼠的CD4+CD25+细胞表达的Foxp3数量增加，并且明显比来自对照抗体处理小鼠的Foxp3具有更强的抑制性。用抗cd25单抗同时使用B细胞耗尽治疗Treg细胞使PGIA的严重程度恢复到与未治疗小鼠相同的水平。虽然自身抗体的滴度没有恢复到未治疗的水平，但CD4+ T细胞对免疫抗原的召回反应通过T细胞增殖和细胞因子产生来测量。因此，B细胞有能力通过增强T效应细胞和抑制Treg细胞来调节炎症反应。
The efficacy of B cell depletion therapy in rheumatoid arthritis (RA) has driven interest in understanding the mechanism. Because the decrease in autoantibododies in RA does not necessarily correlate with clinical outcome other mechanisms may be operative. We previously reported in proteoglycan-induced arthritis (PGIA), B cell depletion inhibits autoreactive T cell responses. Recent studies in B cell depletion therapy also indicate a role for B cells in suppressing regulatory mechanisms. Here we demonstrate that B cells inhibited both the expansion and the function of T regulatory (Treg) cells in PGIA. Utilizing an anti-CD20 mAb, we depleted B cells from mice with PGIA and assessed the Treg cell population. Compared to control antibody-treated mice, Treg cell percentages were elevated in B cell-depleted mice, with a higher proportion of CD4+ T cells expressing Foxp3 and CD25. On a per cell basis, CD4+CD25+ cells from B cell depleted mice expressed increased amounts of Foxp3 and were significantly more suppressive than those from control Ab-treated mice. The depletion of Treg cells with an anti-CD25 mAb concurrent with B cell depletion therapy restored the severity of PGIA to levels equal to untreated mice. Although titers of autoantibodies did not recover to untreated levels, CD4+ T cell recall responses to the immunizing antigen returned as measured by T cell proliferation and cytokine production. Thus, B cells have the capacity to regulate inflammatory responses by enhancing T effector cells along with suppressing Treg cells.
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DOI：
10.4049/jimmunol.0902907
发表时间：
2010-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Doodes PD;Cao Y;Hamel KM;Wang Y;Rodeghero RL;Mikecz K;Glant TT;Iwakura Y;Finnegan A
通讯作者：
Finnegan A
影响因子：
4.4
作者：
Finnegan, A;Grusby, MJ;Zhang, J
通讯作者：
Zhang, J
影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
15.9
作者：
Hu, Chang-Yun;Rodriguez-Pinto, Daniel;Wen, Li
通讯作者：
Wen, Li
影响因子：
--
作者：
Cohen, Stanley B.;Emery, Paul;Totoritis, Mark C.
通讯作者：
Totoritis, Mark C.