Human skin cells support thymus-independent T cell development
Human skin cells support thymus-independent T cell development
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DOI：
10.1172/jci24731
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发表时间：
2005-11-01
影响因子：
15.9
通讯作者：
Kupper, TS
中科院分区：
文献类型：
--
作者：
Clark, RA;Yamanaka, K;Kupper, TS
胸腺组织此前被认为是产生具有功能和多样性的人类T细胞所必需的。我们报道，在没有胸腺组织的情况下，来自人类皮肤的成纤维细胞和角质形成细胞排列在合成的三维基质上，支持从造血祖细胞发展成具有功能的人类T细胞。新生成的T细胞含有T细胞受体切除环，具有多样化的T细胞谱系，功能成熟，对自身MHC具有耐受性，表明成功完成了阳性和阴性选择。皮肤细胞培养表达AIRE、Foxn1和Hoxa3转录因子以及一组自身抗原。因此，皮肤和骨髓活检可以用来产生新的功能和多样化的T细胞群，用于免疫抑制患者的潜在治疗。
Thymic tissue has previously been considered a requirement for the generation of a functional and diverse population of human T cells. We report that fibroblasts and keratinocytes from human skin arrayed on a synthetic 3-dimensional matrix support the development of functional human T cells from hematopoietic precursor cells in the absence of thymic tissue. Newly generated T cells contained T cell receptor excision circles, possessed a diverse T cell repertoire, and were functionally mature and tolerant to self MHC, indicating successful completion of positive and negative selection. Skin cell cultures expressed the AIRE, Foxn1, and Hoxa3 transcription factors and a panel of autoantigens. Skin and bone marrow biopsies can thus be used to generate de novo functional and diverse T cell populations for potential therapeutic use in immunosuppressed patients.