Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama, Kanagawa, Japan.
J Immunol. 2010 Nov 15;185(10):6041-8. doi: 10.4049/jimmunol.0901834. Epub 2010 Oct 6.
The trans presentation of IL-15 by cells expressing the specific high-affinity receptor α-chain (IL-15Rα) to cells expressing the signaling receptor β-chain and γ-chain is essential for the generation and maintenance of CD8 memory T cells, NK cells, and NKT cells in an in vivo mouse system. We have also demonstrated in vitro that cell-surface IL-15Rα on cells expressing all the receptor components present IL-15 to receptor β-chain/γ-chain coexpressed on the same cell surface (cis presentation). However, although mouse CD8 T cells express all the IL-15R components, they show no evidence of cis presentation. In this study, we demonstrate that increased expression of mouse IL-15Rα in mouse CD8 T cells by retrovirus-mediated gene transfer changes the ability of the T cell to use cis presentation on the cell surface, indicating that cis presentation requires high expression of mouse IL-15Rα on the cell surface. Using cell lines expressing human or mouse receptors, we demonstrate that cis presentation occurs more efficiently in the human receptor-ligand combination than in that of the mouse system. Moreover, we found that primary human CD8 T cells do not require trans presentation of human IL-15 in vitro. These findings raise the possibility that the maintenance and generation of memory CD8 T cells are achieved via distinct mechanisms in humans and mice. Therefore, careful study of the human immune system, rather than extrapolation from the murine model, is necessary to achieve more complete understanding of memory CD8 T cell development in humans.
在体内小鼠系统中，表达特异性高亲和力受体 α 链（IL-15Rα）的细胞向表达信号转导受体 β 链和 γ 链的细胞转呈 IL-15 对于 CD8 记忆 T 细胞、NK 细胞和 NKT 细胞的产生和维持至关重要。我们还在体外证明了表达所有受体成分的细胞表面上的细胞表面 IL-15Rα 将 IL-15 呈递给同一细胞表面上表达的受体 β 链/γ 链（顺式呈现）。然而，尽管小鼠 CD8 T 细胞表达所有的 IL-15R 成分，但它们没有顺式呈现的证据。在这项研究中，我们通过逆转录病毒介导的基因转移证明，在小鼠 CD8 T 细胞中增加 IL-15Rα 的表达改变了 T 细胞在细胞表面上使用顺式呈现的能力，表明顺式呈现需要细胞表面上高表达的小鼠 IL-15Rα。使用表达人或鼠受体的细胞系，我们证明顺式呈现发生在人受体-配体组合中比在鼠系统中更有效。此外，我们发现原代人 CD8 T 细胞在体外不需要人 IL-15 的转呈。这些发现提出了这样一种可能性，即记忆 CD8 T 细胞的维持和产生是通过人类和小鼠不同的机制实现的。因此，为了更全面地理解人类记忆 CD8 T 细胞的发育，有必要对人类免疫系统进行仔细研究，而不是从鼠模型推断。
