Regulation of the Expression of CD45 alternative Structures in Lymphocyte Subsets

淋巴细胞亚群中 CD45 替代结构表达的调节

• 批准号: 05670309
• 负责人: NISHIMURA Hiroyuki
• 金额: $ 1.47万
• 依托单位: Toin University of Yokohama (1994)Juntendo University (1993)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670309/
• 关键词: CD45; CD45R; alternative splicing; CD4+ T cells; CD8+ T cells; B cells; differentiation of lymphocytes; lymphocyte subsets; CD45RC; サイトカイン; Th1; Th2; (NZB×N2W)F_1; CD4T細胞

CD45 is a family of membrane-integral protein tyrosine phosphatase thought to be involved in the regulation of signal transduction in lymphocyte. Outer-membrane domain of the molecule has three alternative structures, and eight isoforms are generated by the alternative splicing of exons 4,5 and 6. We analyzed the differential expression of tree CD45 alternative structures (CD45RA,B and C) of mouse CD45 in relation to the ontogeny and differentiation of lymphocyte subsets. The results are summarized as followsB cells : While peripheral B cells were all CD45RA+B+C+, there were differential expressions of these epitopes on bone marrow B lineage cells. Although three alternative CD 45 epitopes began to be expressed at an early stage of pre B cells, the process of each epitope expression differed ; while the expression of CD45RA and CD45RC nearly coincided, CD45RB expression was markedly delayd. Since all three alternative CD45 mRNA expressions occurred at an early pre B cell stage, and pro … More gressively elevated in subsequent developmental stages, the observed delay in the CD45RB expression appeared to be due to post-translational eventsCD4+ T cells : Splenic CD4+ T cells included two populations, CD45RA-B+C- and CD45RA-B+C+. In these cells, messages of alternative exons were associated with either Bone (exon 4 or exon 5) or two exon form (exon 5 and exon 6) of the CD45 transcript.When stimulated by an immobilized CD3 mAb, the CD45RC+CD4+ T cells secreted IL-2 but not other cytokines such as IL-4, IFN-g or IL-10, thereby represented "naive" ThP-type cells. CD45RC-CD4+ T cells produced IL-2, IL-4, IFN-g and IL-10 and likely included both Th1- and Th2-type cells.CD8+ T cells : Splenic CD8+ T cells were separated into CD45RA-B+C+ and CD45RA+B+C+. There were transcripts with one, two, or three alternative exons suggesting that these cells express various types of CD45 isoforms including the largest form with all three alternative structures. Studies on T cell clones established in vitro revealed that while cytotoxic CD8+ T cells clones were CD45RA+, suppressor effecter CD8+ T cell clones were CD45RA-. Further studies on the functional difference between CD45RA-CD8+ T cells and CD45RA+CD8+ T cells are in progress. Less

CD45是一种膜综合蛋白酪氨酸磷酸酶家族，被认为与淋巴细胞信号转导的调节有关。该分子的外膜结构域具有三个替代结构，通过外显子4,5和6的替代剪接产生了八种同工型。我们分析了小鼠CD45的树CD45替代结构（CD45RA，B和C）的差异表达与小鼠CD45的lymphopphopphopphopphopphopphocetete subsets cd45相关。结果总结如下：虽然周围B细胞都是CD45RA+B+C+，但这些表位在骨髓B谱系细胞上存在差异表达。尽管三个替代CD 45表位开始在B细胞的早期阶段表达，但每个表位表达的过程都不同。尽管CD45RA和CD45RC的表达几乎重合，但CD45RB表达明显延迟。由于所有三种替代CD45 mRNA表达式都发生在B细胞前的早期阶段，并且在随后的发育阶段中更加可观的升高，因此观察到的CD45RB表达的延迟似乎是由于翻译后事件CD4+T细胞：脾脏CD4+T细胞：CD45RA-B+C-C-+C-+C-+C-B+C+C+C+C+C+C+CCD4+T细胞。在这些细胞中，替代外显子的信息与CD45转录本的骨头（外显子4或外显子5）或两种外显子形式（外显子5和外显子6）相关。 CD45RC-CD4+ T细胞产生了IL-2，IL-4，IFN-G和IL-10，可能包括Th1-和Th2型细胞。CD8+ T细胞：脾脏CD8+ T细胞分离为CD45RA-B+ C+ C+和CD45RA+ B+ C+ C+ CD45RA-B+ C+ C+和CD45RA-B+ C+。有一个，两个或三个替代外显子的转录本，表明这些细胞表达各种类型的CD45同工型，包括所有三种替代结构的最大形式。在体外建立的T细胞克隆的研究表明，虽然细胞毒性CD8+ T细胞克隆是CD45RA+，但抑制效应子CD8+ T细胞克隆是CD45RA-。进一步研究CD45RA-CD8+ T细胞和CD45RA+ CD8+ T细胞之间的功能差异正在进行中。较少的

项目成果

H.Nishimura et al.: "Differential expression of three CD45 alternative structures on murine T cells" Int.Immunol.4. 923-930 (1992)

H.Nishimura 等人：“小鼠 T 细胞上三种 CD45 替代结构的差异表达”Int.Immunol.4。

Inoue T,Asano Y,Matsuoka Furutani-Seiki M,Aizawa S,Nishimura H,Shirai T,Tada T:"Distinction of mouse CD8^+ suppressor effector T cell clones from cytotoxic T cell clones by cytokine production and CD45 isoforms." J.Immunol.150. 2121-2128 (1993)

Inoue T、Asano Y、Matsuoka Furutani-Seiki M、Aizawa S、Nishimura H、Shirai T、Tada T：“通过细胞因子产生和 CD45 亚型区分小鼠 CD8^ 抑制效应 T 细胞克隆与细胞毒性 T 细胞克隆。”

H.Nishimura et al.: "Differential expression of a CD45R epitope(6B2)on murine CD5+ B cells" Cell.Immunol.140. 432-443 (1992)

H.Nishimura 等人：“鼠 CD5 B 细胞上 CD45R 表位 (6B2) 的差异表达”Cell.Immunol.140。

Inoue,T.et al.: "Distinction of mouse CD8^+ suppressor effector T cell clones from cytotoxic T cell clones by cytokine production and CD45 isoforms." J.Immunol.150. 2121-2128 (1993)

Inoue,T.et al.：“通过细胞因子产生和 CD45 亚型区分小鼠 CD8^ 抑制效应 T 细胞克隆与细胞毒性 T 细胞克隆。”

Nishimura H,Hattori S,Abe M,Ueda G,Okamoto H,Tsurui S,Hirose S,Shirai T:"Differntial expression of three CD45 alternative structures on murine T cells:exon 6-dependent epitope as a marker for functional heterogeneity of CD4^+ T cells." Int.Immunol.4. 923-

Nishimura H、Hattori S、Abe M、Ueda G、Okamoto H、Tsurui S、Hirose S、Shirai T：“小鼠 T 细胞上三种 CD45 替代结构的差异表达：外显子 6 依赖性表位作为 CD4 功能异质性的标记