IL-15 and dermal fibroblasts induce proliferation of natural regulatory T cells isolated from human skin
IL-15 and dermal fibroblasts induce proliferation of natural regulatory T cells isolated from human skin
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DOI：
10.1182/blood-2006-02-002873
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发表时间：
2007-01-01
期刊：
影响因子：
20.3
通讯作者：
Kupper, Thomas S.
中科院分区：
文献类型：
--
作者：
Clark, Rachael A.;Kupper, Thomas S.
调节性T细胞(Treg)对于诱导和维持自身耐受性至关重要，在正常、非炎症条件下存在于皮肤和肠道等外周组织中。我们报告了居住在正常人皮肤上的Treg种群的隔离和扩大。皮肤Treg高水平表达CD25、L-选择素、GITR、FOXP3和细胞内CTLA-4，低水平表达CD69，高水平表达皮肤归巢寻址蛋白CLA、CCR4和CCR6。皮肤树突状细胞抑制CD3和CD28抗体对同一皮肤样本中CD25(Lo)T细胞的增殖。抑制作用依赖于细胞接触，不受白介素10(IL-10)和转化生长因子-β(TGF-β)中和抗体的影响。令人惊讶的是，当皮肤Tregs与真皮成纤维细胞和IL-15接触时，皮肤Treg以不依赖于抗原的方式增殖，这种情况类似于在慢性炎症皮肤中发现的情况。我们假设Tregs的局部增殖可能发生在发炎的皮肤中，可以作为皮肤炎症的刹车，以及在完整生物体中观察到的天然Tregs的动态平衡增殖的机制。
Regulatory T cells (Tregs) are crucial for the induction and maintenance of self-tolerance and are present in peripheral tissues such as skin and gut under normal, noninflamed conditions. We report isolation and expansion of the Treg population resident in normal human skin. Cutaneous Tregs expressed high levels of CD25, L-selectin, GITR, FOXP3, and intracellular CTLA-4, low levels of CD69, and high levels of the skin-homing addressins CLA, CCR4, and CCR6. Skin Tregs suppressed the proliferation of CD25(lo) T cells from the same skin sample in response to CD3 and CD28 antibodies. Suppression was dependent on cell contact and not affected by neutralizing antibodies to interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta). Surprisingly, cutaneous Tregs proliferated in an antigen-independent manner when cultured in contact with dermal fibroblasts and IL-15, conditions similar to those found in chronically inflamed skin. We hypothesize that local proliferation of Tregs may occur within inflamed skin and could serve as a brake for cutaneous inflammation as well as a mechanism for the homeostatic proliferation of natural Tregs that has been observed within intact organisms.