Dysfunctional blood and target tissue CD4+CD25high regulatory T cells in psoriasis:: Mechanism underlying unrestrained pathogenic effector T cell proliferation
Dysfunctional blood and target tissue CD4+CD25high regulatory T cells in psoriasis:: Mechanism underlying unrestrained pathogenic effector T cell proliferation
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DOI：
10.4049/jimmunol.174.1.164
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发表时间：
2005-01-01
影响因子：
4.4
通讯作者：
Cooper, KD
中科院分区：
文献类型：
--
作者：
Sugiyama, H;Gyulai, R;Cooper, KD
调节和效应功能之间的平衡对于维持有效的免疫应答，同时避免自身免疫是重要的。炎症性皮肤病银屑病是持续的病原性效应T细胞的激活。我们发现，外周血中的CD 4（+）T淋巴细胞亚群，表型为CD 25（高），CTLA-4（+），Foxp 3（高）（调节性T（Treg）细胞），在银屑病中缺乏其抑制活性。这与银屑病中CD 4（+）应答T细胞的加速增殖有关，其中大部分表达CXCR 3。然而，交叉实验将缺陷分离到银屑病Treg细胞。为了检查人T细胞介导的疾病的非淋巴组织中的Treg细胞，还分析了Treg细胞，并从炎症部位、银肩病皮损皮肤分离Treg细胞。然而，在经计算存在于皮肤中的调节性T细胞与效应性T细胞的比率下，银肩病Treg细胞群体显示出对效应性T细胞的抑制降低。因此，功能失调的血液和靶组织CD 4（+）CD 25（高）Treg细胞活性可能导致体内银屑病病原性T细胞的抑制减少和随后的过度增殖。这些发现代表了人类器官特异性自身免疫性疾病的关键组成部分，并可能对体内Treg细胞的可能治疗操作具有重要意义。
The balance between regulatory and effector functions is important for maintaining efficient immune responses, while avoiding autoimmunity. The inflammatory skin disease psoriasis is sustained by the ongoing activation of pathogenic effector T cells. We found that a CD4(+) T lymphocyte subpopulation in peripheral blood, phenotypically CD25(high), CTLA-4(+), Foxp3(high) (regulatory T (Treg) cells), is deficient in its suppressor activity in psoriasis. This was associated with accelerated proliferation of CD4(+) responder T cells in psoriasis, the majority of which expressed CXCR3. Nevertheless, criss-cross experiments isolated the defect to psoriatic Treg cells. To examine Treg cells in a nonlymphoid tissue of a human T cell-mediated disease, Treg cells were also analyzed and isolated from the site of inflammation, psoriatic lesional skin. At the regulatory vs effector T cells ratios calculated to be present in skin, however, the psoriatic Treg cell population demonstrated decreased suppression of effector T cells. Thus, dysfunctional blood and target tissue CD4(+)CD25(high) Treg cell activity may lead to reduced restraint and consequent hyperproliferation of psoriatic pathogenic T cells in vivo. These findings represent a critical component of human organ-specific autoimmune disease and may have important implications with regard to the possible therapeutic manipulation of Treg cells in vivo.