Increased TGF‐β–producing CD4+ T lymphocytes in postburn patients and their potential interaction with dermal fibroblasts in hypertrophic scarring
Increased TGF‐β–producing CD4+ T lymphocytes in postburn patients and their potential interaction with dermal fibroblasts in hypertrophic scarring
复制标题
DOI：
10.1111/j.1524-475x.2007.00261.x
复制
发表时间：
2007-07
影响因子：
2.9
通讯作者：
Jianfei Wang;Haiyan Jiao;T. Stewart;H. Shankowsky;P. Scott;E. Tredget
中科院分区：
文献类型：
--
作者：
Jianfei Wang;Haiyan Jiao;T. Stewart;H. Shankowsky;P. Scott;E. Tredget
增生性瘢痕的发展涉及细胞和细胞因子之间复杂的相互作用。虽然其发病机制尚未完全了解，但已报道了极化的辅助性T细胞2型免疫应答，表明CD 4 + T淋巴细胞在增生性瘢痕形成中的作用。在这里，我们报告了烧伤患者外周血和增生性瘢痕组织中产生CD 4 +/转化生长因子-β（TGF-β）的T细胞的频率增加。这些细胞可能通过影响真皮成纤维细胞的功能而对增生性瘢痕起间接调节作用。我们的研究结果表明，增加细胞增殖和胶原蛋白合成的真皮成纤维细胞与烧伤患者的CD 4 + T淋巴细胞，但不是从正常人的CD 4 + T细胞来源的培养基处理。使用共聚焦显微镜和免疫印迹，我们发现在这些处理的真皮成纤维细胞中α-平滑肌肌动蛋白的水平升高，这也显示出收缩胶原晶格的能力增强。烧伤患者CD 4 + T淋巴细胞条件培养液中TGF-β水平显著高于正常人CD 4 + T淋巴细胞条件培养液中TGF-β水平。此外，TGF-β中和抗体的应用显著降低了烧伤患者CD 4 + T淋巴细胞培养基对真皮成纤维细胞增殖和胶原晶格收缩的影响。我们的研究表明，产生CD 4 +/TGF-β的T淋巴细胞可能在烧伤后增生性瘢痕形成中起重要作用。
The development of hypertrophic scar involves a complex interplay between cells and cytokines. Although the mechanism underlying its pathogenesis is not well understood, a polarized T‐helper type 2 immune response has been reported, indicating a role for CD4+ T lymphocytes in hypertrophic scarring. Here, we report an increased frequency of CD4+/transforming growth factor‐β (TGF‐β)‐producing T cells in the peripheral blood and hypertrophic scar tissue of burn patients. These cells may play an indirect regulatory role in hypertrophic scar by affecting the functions of dermal fibroblasts. Our results show an increase in cell proliferation and collagen synthesis by dermal fibroblasts treated with medium derived from burn patient CD4+ T lymphocytes but not from the CD4+ T cells of normal subjects. Using confocal microscopy and immunoblotting, we found the level of α‐smooth muscle actin to be elevated in these treated dermal fibroblasts, which also showed an enhanced ability to contract collagen lattices. TGF‐β levels in medium conditioned by the culture of CD4+ T lymphocytes from burn patients were significantly higher than in the conditioned medium from CD4+ T lymphocytes of normal subjects. In addition, the application of a TGF‐β–neutralizing antibody significantly reduced the effect of burn patient CD4+ T lymphocyte medium on dermal fibroblast proliferation and collagen lattice contraction. Our study suggests that CD4+/TGF‐β–producing T lymphocytes may play an important role in postburn hypertrophic scarring.