Suwa H, Tanaka T, Kitamura F, Shiohara T, Kuida K, Miyasaka M
Department of Immunology, Tokyo Metropolitan Institute of Medical Science, Japan.
Int Immunol. 1995 Sep;7(9):1441-9. doi: 10.1093/intimm/7.9.1441.
The IL-2 receptor beta-chain (IL-2R beta), a specificity-determining subunit in the IL-2R complex with a restricted tissue distribution pattern, is essential for signal transduction. Our previous studies demonstrate that the continuous treatment of mice with anti-IL-2R beta resulted in the complete disappearance of NK cells and Thy-1+ dendritic epidermal cells (Thy-1+ dEC), suggesting that signals through IL-2R beta are critically involved in development of these lymphocyte subsets. However, these lymphocyte subsets are reported to be apparently unaffected in the IL-2-deficient mice. To further examine the biological roles of the IL-2R beta, transgenic mice carrying the IL-2R beta transgene were generated. In these mice, high levels of the cell surface expression of the IL-2R beta were observed in essentially all hematopoietic lineage cells, and CD4+ T cells as well as CD8+ T cells showed vigorous cell proliferation upon IL-2 stimulation. Surprisingly, NK cells marked with a high expression of NK1.1 in the spleen and Thy-1+ dEC in the skin were completely absent in transgenic mice. However, the development of other lymphocyte subsets including conventional alpha beta TCR+ cells, gamma delta TCR+ cells and B cells remained apparently intact. From these observations together with previous data on IL-2-deficient mice, we speculate that factors, other than IL-2 that utilizes the IL-2R beta as its functional receptor subunit, may have a vital role in the development of NK cells and Thy-1+ dEC. Implications for possible in vivo functions of over-expressed IL-2R beta are discussed.
白细胞介素-2受体β链（IL-2Rβ）是IL-2受体复合物中决定特异性的亚基，其组织分布模式有限，对信号转导至关重要。我们之前的研究表明，用抗IL-2Rβ持续治疗小鼠会导致自然杀伤细胞（NK细胞）和Thy-1⁺树突状表皮细胞（Thy-1⁺ dEC）完全消失，这表明通过IL-2Rβ的信号在这些淋巴细胞亚群的发育中起关键作用。然而，据报道这些淋巴细胞亚群在IL-2缺陷小鼠中明显未受影响。为了进一步研究IL-2Rβ的生物学作用，我们构建了携带IL-2Rβ转基因的转基因小鼠。在这些小鼠中，基本上所有造血谱系细胞都观察到IL-2Rβ在细胞表面高水平表达，并且CD4⁺ T细胞和CD8⁺ T细胞在IL-2刺激下显示出旺盛的细胞增殖。令人惊讶的是，在转基因小鼠中，脾脏中高表达NK1.1的NK细胞和皮肤中的Thy-1⁺ dEC完全缺失。然而，包括传统的αβ TCR⁺细胞、γδ TCR⁺细胞和B细胞在内的其他淋巴细胞亚群的发育似乎仍保持完整。结合之前关于IL-2缺陷小鼠的数据，我们推测除了以IL-2Rβ作为其功能性受体亚基的IL-2之外，其他因素可能在NK细胞和Thy-1⁺ dEC的发育中起重要作用。本文还讨论了过表达的IL-2Rβ可能的体内功能。
