Human keratinocyte induction of rapid effector function in antigen-specific memory CD4+ and CD8+ T cells
Human keratinocyte induction of rapid effector function in antigen-specific memory CD4+ and CD8+ T cells
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DOI：
10.1002/eji.200636915
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发表时间：
2007-06-01
影响因子：
5.4
通讯作者：
Ogg, Graham S.
中科院分区：
文献类型：
--
作者：
Black, Antony P. B.;Ardern-Jones, Michael R.;Ogg, Graham S.
人类角质形成细胞向 T 细胞呈递抗原的能力存在争议，事实上，有人认为角质形成细胞可能会促进 T 细胞反应低下。此外，尚不清楚角质形成细胞是否可以在 MHC I 类和 II 类呈递之前处理抗原。我们使用肽、蛋白质和重组表达载体作为抗原来源，测试了角质形成细胞在表位特异性 CD4(+) 和 CD8(+) 记忆 T 细胞中诱导功能反应的能力。角质形成细胞能够有效地处理并向 CD4+ T 细胞呈递蛋白质抗原，从而导致细胞因子分泌（Th1 和 Th2）。这种相互作用依赖于 HLA II 类和 ICAM-1 的角质形成细胞表达，而 IFN-7 可以诱导这种表达。此外，角质形成细胞可以将病毒编码的或外源的肽呈递给CD8+T细胞，导致T细胞细胞因子的产生和靶细胞裂解。最后，使用角质形成细胞作为刺激物生长的 T 细胞系没有表现出功能丧失。这些发现表明角质形成细胞能够有效地处理并向 CD4(+) 和 CD8(+) 记忆 T 细胞呈递抗原并诱导功能反应。这些发现对皮肤疾病的发病机制以及经皮药物或疫苗输送具有广泛的影响。
The ability of human keratinocytes to present antigen to T cells is controversial and, indeed, it has been suggested that keratinocytes may promote T cell hyporesponsiveness. Furthermore, it is unclear whether keratinocytes can process antigen prior to MHC class I and class II presentation. We tested the ability of keratinocytes to induce functional responses in epitope-specific CD4(+) and CD8(+) memoryTcells usingpeptides, protein and recombinant expression vectors as sources of antigen. Keratinocytes were able to efficiently process and present protein antigen to CD4+ T cells, resulting in cytokine secretion (Th1 and Th2). This interaction was dependent on keratinocyte expression of HLA class II and ICAM-1, which could be induced by IFN-7. In addition, keratinocytes could present virally encoded or exogenous peptide to CD8(+) T cells resulting in T cell cytokine production and target cell lysis. Finally, T cell lines grown using keratinocytes as stimulators showed no loss of function. These findings demonstrate that keratinocytes are able to efficiently process and present antigen to CD4(+) and CD8(+) memory T cells and induce functional responses. The findings have broad implications for the pathogenesis of cutaneous disease and for transcutaneous drug or vaccine delivery.