Clark Rachael A, Chong Benjamin, Mirchandani Nina, Brinster Nooshin K, Yamanaka Kei-Ichi, Dowgiert Rebecca K, Kupper Thomas S
Department of Dermatology, Brigham and Women's Hospital and Harvard Skin Disease Research Center, Boston, MA 02115, USA.
J Immunol. 2006 Apr 1;176(7):4431-9. doi: 10.4049/jimmunol.176.7.4431.
There are T cells within normal, noninflamed skin that most likely conduct immunosurveillance and are implicated in the development of psoriasis. We isolated T cells from normal human skin using both established and novel methods. Skin resident T cells expressed high levels of CLA, CCR4, and CCR6, and a subset expressed CCR8 and CXCR6. Skin T cells had a remarkably diverse TCR repertoire and were mostly Th1 memory effector cells with smaller subsets of central memory, Th2, and functional T regulatory cells. We isolated a surprising number of nonexpanded T cells from normal skin. To validate this finding, we counted T cells in sections of normal skin and determined that there are approximately 1 x 10(6) T cells/cm(2) normal skin and an estimated 2 x 10(10) T cells in the entire skin surface, nearly twice the number of T cells in the circulation. Moreover, we estimate that 98% of CLA(+) effector memory T cells are resident in normal skin under resting conditions. These findings demonstrate that there is a large pool of memory T cells in normal skin that can initiate and perpetuate immune reactions in the absence of T cell recruitment from the blood.
在正常的、未发炎的皮肤中存在T细胞,这些T细胞很可能进行免疫监视并与银屑病的发生有关。我们使用既定方法和新方法从正常人皮肤中分离出T细胞。皮肤驻留T细胞高水平表达CLA、CCR4和CCR6,并且有一个亚群表达CCR8和CXCR6。皮肤T细胞具有非常多样化的TCR库,并且大多是Th1记忆效应细胞,还有较小比例的中枢记忆细胞、Th2细胞和功能性调节性T细胞亚群。我们从正常皮肤中分离出数量惊人的未扩增T细胞。为了验证这一发现,我们对正常皮肤切片中的T细胞进行计数,确定正常皮肤中约有1×10⁶个T细胞/cm²,整个皮肤表面估计有2×10¹⁰个T细胞,几乎是循环中T细胞数量的两倍。此外,我们估计在静息状态下,98%的CLA⁺效应记忆T细胞驻留在正常皮肤中。这些发现表明,正常皮肤中存在大量记忆T细胞库,在没有从血液中招募T细胞的情况下,这些T细胞能够启动并维持免疫反应。