Activated CD4+ T cells target mesangial antigens and initiate glomerulonephritis.
Activated CD4+ T cells target mesangial antigens and initiate glomerulonephritis.
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DOI：
10.1159/000342368
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Bagavant H
中科院分区：
文献类型：
--
作者：
Scindia Y;Nackiewicz D;Dey P;Szymula A;Bajwa A;Rosin DL;Bolton WK;Okusa MD;Deshmukh U;Bagavant H
肾脏浸润性T细胞在狼疮性肾炎病理中的作用尚不清楚。本研究旨在探讨CD4 + T细胞对替代系膜抗原的反应是否可以引发肾小球肾炎。用抗α 8整合素免疫脂质体（α 8 ILs）将卵清蛋白沉积于C57BL/6（B6）小鼠肾小球系膜。随后注射活化的卵清蛋白反应性CD4+转基因OT2 T细胞。通过流式细胞术研究抗原特异性OT2 T细胞向肾和淋巴结的运输。肾小球病理和免疫细胞浸润的特点是免疫染色。使用B6.ccr2 −/−小鼠研究了CCR 2缺陷对T细胞介导的肾小球肾炎的作用。α 8 IL将卵清蛋白特异性地递送到肾小球。连续转移的OT2 T细胞优先积聚在肾淋巴结和肾皮质中。肾脏显示肾小球炎症，伴有内源性T细胞、树突状细胞和巨噬细胞的募集。T细胞介导的炎症诱导系膜细胞活化和肾小球MCP 1和纤维连接蛋白的增加。炎症灶的形成由Ly6C单核细胞驱动，并且是CCR2依赖性的。这项研究的结果表明，与系膜抗原反应的T细胞足以引发肾小球病理。抗原特异性CD4 T细胞通过诱导肾小球MCP 1产生而起作用，MCP 1介导炎症单核细胞的募集，导致肾小球肾炎。因此，下调狼疮患者肾脏内的T细胞应答将是一种有益的治疗方法。
The role of kidney infiltrating T cells in the pathology of lupus nephritis is unclear. This study was undertaken to investigate whether CD4+ T cell responses to a surrogate mesangial antigen can initiate glomerulonephritis. Ovalbumin was deposited in the glomerular mesangium of C57BL/6 (B6) mice using anti-α8 integrin immunoliposomes (α8ILs). This was followed by injection of activated ovalbumin-reactive CD4+ transgenic OT2 T cells. Trafficking of antigen-specific OT2 T cells to kidneys and lymph nodes was studied by flow cytometry. Glomerular pathology and immune cell infiltration was characterized by immunostaining. Role of CCR2 deficiency on T cell mediated glomerulonephritis was investigated using B6.ccr2−/− mice. α8ILs delivered ovalbumin specifically to the renal glomeruli. Adoptively transferred OT2 T cells preferentially accumulated in renal lymph nodes and in the renal cortex. Kidneys showed glomerular inflammation with recruitment of endogenous T cells, dendritic cells and macrophages. T cell mediated inflammation induced mesangial cell activation and an increase in glomerular MCP1 and fibronectin. The formation of inflammatory foci was driven by Ly6C monocytes and was CCR2 dependent. The findings from this study show that T cells reactive with antigens in the mesangium are sufficient to initiate glomerular pathology. Antigen-specific CD4 T cells act by inducing glomerular MCP1 production which mediates recruitment of inflammatory monocytes resulting in glomerulonephritis. Thus, down modulation of T cell responses within the kidneys of lupus patients will be a beneficial therapeutic approach.
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影响因子：
16.1
作者：
Scindia, Yogesh M.;Deshmukh, Umesh S.;Bagavant, Harini
通讯作者：
Bagavant, Harini
影响因子：
19.6
作者：
COUCHMAN, JR;BEAVAN, LA;MCCARTHY, KJ
通讯作者：
MCCARTHY, KJ
DOI：
10.1073/pnas.91.7.2752
发表时间：
1994-03-29
影响因子：
11.1
作者：
CHARO, IF;MYERS, SJ;COUGHLIN, SR
通讯作者：
COUGHLIN, SR
影响因子：
6
作者：
Bagavant, Harini;Scindia, Yogesh;McNamara, Coleen
通讯作者：
McNamara, Coleen
影响因子：
4
作者：
Barnden, MJ;Allison, J;Carbone, FR
通讯作者：
Carbone, FR