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

CD 45是一个膜整合蛋白酪氨酸磷酸酶家族，被认为参与淋巴细胞信号转导的调节。该分子的外膜结构域具有三种选择性结构，通过外显子4、5和6的选择性剪接产生八种异构体。我们分析了小鼠CD 45的三种替代结构（CD 45 RA、B和C）的差异表达与个体发育和淋巴细胞亚群分化的关系。B细胞：外周血B细胞均为CD 45 RA +B+C+，而骨髓B细胞上存在这些表位的差异表达。虽然前B细胞早期即开始表达CD 45的3个替代表位，但各表位表达的过程不同，CD 45 RA和CD 45 RC的表达几乎一致，而CD 45 RB的表达明显延迟。由于所有三种不同的CD 45 mRNA表达都发生在早期前B细胞阶段， ...更多信息 CD 4 + T细胞：脾CD 4 + T细胞包括两个群体，CD 45 RA-B +C-和CD 45 RA-B +C+。在这些细胞中，交替外显子的信息与Bone（外显子4或外显子5）或两个外显子形式（外显子5和外显子6）的CD 45转录本相关，当被固定化的CD 3 mAb刺激时，CD 45 RC + CD 4 + T细胞分泌IL-2，而不分泌其他细胞因子如IL-4、IFN-g或IL-10，因此代表“幼稚”ThP型细胞。CD 45 RC-CD 4 + T细胞产生IL-2、IL-4、IFN-g和IL-10，并且可能包括Th 1型和Th 2型细胞。CD 8 + T细胞：将脾CD 8 + T细胞分离成CD 45 RA-B +C+和CD 45 RA +B+C+。存在具有一个、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CD 45同种型，包括具有所有三种替代结构的最大形式。对体外建立的T细胞克隆的研究表明，细胞毒性CD 8 + T细胞克隆为CD 45 RA+，而抑制效应CD 8 + T细胞克隆为CD 45 RA-。关于CD 45 RA-CD 8 + T细胞和CD 45 RA + CD 8 + T细胞之间的功能差异的进一步研究正在进行中。少

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。”

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。”

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。

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