Role of CD4+CD25+ T regulatory cells in IL-2-induced vascular leak
Role of CD4+CD25+ T regulatory cells in IL-2-induced vascular leak
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DOI：
10.1093/intimm/dxl079
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发表时间：
2006-10-01
影响因子：
4.4
通讯作者：
Nagarkatti, Mitzi
中科院分区：
文献类型：
--
作者：
Melencio, Louise;McKallip, Robert J.;Nagarkatti, Mitzi
T调节性细胞(CD4（+)CD25(+)）在调节免疫应答中发挥重要作用。然而，对于T调节性细胞在IL-2激活淋巴细胞后调节内皮细胞（EC）损伤的能力知之甚少。因此，在当前的研究中，我们使用具有良好特征的C57BL/6 （T(h)1偏倚）和BALB/c （T(h)2偏倚）模型，研究了T调节细胞和随后的T(h)1/T(h)2偏倚在il -2介导的EC损伤中的作用。IL-2治疗后，BALB/c小鼠对IL-2诱导的血管渗漏综合征（VLS）的易感性较C57BL/6小鼠低。与C57BL/6小鼠相比，BALB/c小鼠脾细胞对ECs的细胞毒性较小。有趣的是，与C57BL/6小鼠的CD4(+)CD25(+) T调节细胞相比，BALB/c小鼠的CD4(+)CD25(+) T调节细胞在IL-2治疗后增殖更深刻。此外，来自BALB/c小鼠的T调节细胞比来自C57BL/6小鼠的类似细胞更有效地抑制抗cd3单抗刺激的T细胞增殖。在BALB/c和C57BL/6小鼠中，T调节细胞的缺失导致il -2诱导的VLS显著增加。综上所述，本研究结果提示CD4(+)CD25(+) T调节细胞在il -2诱导的EC损伤中发挥重要作用。
T regulatory cells (CD4(+)CD25(+)) play an important role in the regulation of the immune response. However, little is known about the ability of T regulatory cells to regulate endothelial cell (EC) damage following activation of lymphocytes with IL-2. Therefore, in the current study, we examined the role of T regulatory cells and the subsequent T(h)1/T(h)2 bias in IL-2-mediated EC injury using the well-characterized C57BL/6 (T(h)1-biased) and BALB/c (T(h)2-biased) models. Following IL-2 treatment, BALB/c mice were less susceptible to IL-2-induced vascular leak syndrome (VLS) compared with C57BL/6 mice. Splenocytes from BALB/c mice displayed less cytotoxicity against ECs compared with those from C57BL/6 mice. Interestingly, BALB/c mice had significantly higher numbers of CD4(+)CD25(+) T regulatory cells, which proliferated more profoundly following IL-2 treatment, compared with CD4(+)CD25(+) T regulatory cells from C57BL/6 mice. In addition, T regulatory cells from naive BALB/c mice were more potent suppressors of anti-CD3 mAb-stimulated proliferation of T cells than similar cells from C57BL/6 mice. Depletion of T regulatory cells in both BALB/c and C57BL/6 mice led to a significant increase in IL-2-induced VLS. Together, the results from this study suggest that CD4(+)CD25(+) T regulatory cells play an important role in the regulation of IL-2-induced EC injury.