IL-2/anti-IL-2 antibody complex treatment inhibits the development but not the progression of herpetic stromal keratitis.

IL-2/anti-IL-2 antibody complex treatment inhibits the development but not the progression of herpetic stromal keratitis.
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DOI:
10.4049/jimmunol.1401285
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发表时间:
2015-01-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Suvas S
Suvas S
中科院分区:
其他
文献类型:
--
作者:
Gaddipati S;Estrada K;Rao P;Jerome AD;Suvas S

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白细胞介素-2 (IL-2)和抗IL-2抗体免疫复合物最近被证明可以扩大自然发生的CD4+Foxp3+调节性T细胞(Foxp3+ Tregs)池。在本报告中,我们发现,在角膜单纯疱疹病毒-1 (HSV-1)感染之前,给C57BL/6小鼠注射IL-2/抗IL-2抗体免疫复合物,在感染后的早期时间点测量Foxp3+ Tregs库,显著增加。感染后第2天和第4天Foxp3+ treg数量的增加导致严重HSK的发展明显减少。与对照组的角膜相比,免疫复合物处理组的角膜在感染后第2天的感染性病毒数量显著减少,但在感染后第4天没有。降低病毒载量与免疫复合物处理组小鼠角膜NK细胞数量增加两倍相关。此外,在免疫复合物治疗组感染小鼠感染后的第7天和第16天,检测到炎症角膜中CD4 T细胞的流入急剧减少。在感染后第5、6、7天给予免疫复合物治疗可显著增加引流淋巴结和脾脏中的Foxp3+ Tregs,但不能降低HSK的严重程度。在感染后第16天,两组小鼠的CD4 T细胞和粒细胞流入炎症角膜方面没有显著差异。我们的研究结果表明,在继发性淋巴组织感染后早期而不是晚期增加Foxp3+ Tregs对控制HSK的严重程度更有效。
Interleukin-2 (IL-2) and anti-IL-2 antibody immune complex has recently been shown to expand the naturally occurring pool of CD4+Foxp3+ regulatory T cells (Foxp3+ Tregs). In this report, we showed that administration of IL-2/anti-IL-2 antibody immunocomplex to C57BL/6 mice, prior to corneal herpes simplex virus-1 (HSV-1) infection, significantly increased the pool of Foxp3+ Tregs when measured at early time-points post-infection. Increased numbers of Foxp3+ Tregs on day 2 and day 4 post-infection resulted in a marked reduction in the development of severe HSK. When compared to corneas from the control group, corneas from the immunocomplex-treated group showed a significant reduction in the amount of infectious virus on day 2 but not on day 4 post-infection. Reduced viral load was associated with two-fold increase in NK cell numbers in corneas from the immunocomplex-treated group of mice. Moreover, a dramatic reduction in the influx of CD4 T cells in inflamed corneas was determined on days 7 and 16 post-infection in the immunocomplex-treated group of infected mice. Immunocomplex treatment given on days 5, 6 and 7 post-infection significantly increased Foxp3+ Tregs in draining lymph nodes and in the spleen but failed to reduce the severity of HSK. In terms of the influx of CD4 T cells and granulocytes into inflamed corneas, no significant differences were noted between both groups of mice on day 16 post-infection. Our findings demonstrate that increasing Foxp3+ Tregs early but not late after infection in secondary lymphoid tissues is more efficacious in controlling the severity of HSK.
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