The Role of CD45 in Leukocyte Differentiation and Function

CD45 在白细胞分化和功能中的作用

• 批准号: 06044178
• 负责人: KISHIHARA Kenji
• 金额: $ 3.52万
• 依托单位: KYUSHU UNEVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for international Scientific Research
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06044178/
• 关键词: CD45; Tyrosine Phosphatase; T cell; B cell; NK cell; Gene Targeting; 白血球; 免疫異常

We have analyzed the involvement of CD45 in development, activation and function of T,B and NK cells using CD45 exon 6-deficient mice (CD45-/-mice) in this research project.In the analysis of CD45-deicient T cell receptor (TCR)-transgenic CD45 mice, it was suggested that CD45 is involved in the signal transduction for positive selection of T cells and allelic exclusion of TCRalpha chain. CD45-defective thymocytes and peripheral mature T cells from CD45-/- mice showed virtually no response to TCR-crosslinking suggesting that CD45 is crucial for a TCR-mediated signaling mechanism. Furthermore, Antigen-specific response including cytolytic T lymphocyte and helper T cell function could not observed in CD45^- T cells from CD45-/- mice. Moreover, it was demonstrated that CD45 is involved in the signal transduction during maturation of Vgamma3 T cells in epidermis and fetal thymus.B cell development in the CD45-/- mice was enhanced throughout their lives (the approximately twice more increased number of B cells (sIgM^+) in the spleen). CD45-defective B cells from CD45-/-mice showed intact B cell functions including T -dependent and -independent antigen-specific antibody production and class switching in vivo if normal CD4^+ T cells were adoptively transferred into the knock out mice.The NK activity of the splenocytes from CD45-/- mice was markedly elevated because of the increased number of NK cells in the CD45-/- mice. Cytolytic and ADCC activities were intact in the NK and LAK cells despite no CD45 surface expression.From the above data, it's clear that requirement of CD45 for development and function is different in T,B and NK cells.

本研究利用CD 45外显子6缺陷小鼠（CD 45-/-mice）研究了CD 45在T、B和NK细胞发育、活化和功能中的作用，在CD 45缺陷型T细胞受体（TCR）转基因CD 45小鼠的研究中，发现CD 45参与了T细胞的正向选择和TCR α链的等位基因排斥的信号转导。来自CD 45-/-小鼠的CD 45缺陷型胸腺细胞和外周成熟T细胞显示对TCR交联几乎没有反应，表明CD 45对于TCR介导的信号传导机制是至关重要的。此外，在来自CD 45-/-小鼠的CD 45 ^- T细胞中未观察到抗原特异性反应，包括溶细胞性T淋巴细胞和辅助性T细胞功能。此外，研究表明，CD 45参与了表皮和胎儿胸腺中V γ 3 T细胞成熟过程中的信号转导。CD 45-/-小鼠的B细胞发育在其一生中得到增强（脾脏中B细胞（sIgM^+）的数量增加了约两倍）。如果将正常的CD 4 ^+ T细胞过继转移到敲除小鼠中，则来自CD 45-/-小鼠的CD 45缺陷型B细胞显示完整的B细胞功能，包括T依赖性和非依赖性抗原特异性抗体产生和体内类别转换。NK细胞和LAK细胞表面不表达CD 45，但其细胞溶解活性和ADCC活性不变，说明T、B细胞和NK细胞对CD 45的发育和功能的需要是不同的。

项目成果

Valerie A.Wallace: "Alterations in the Level of CD45 Surface Expression Affect the Outcome of Thymic Selection" (投稿中).

Valerie A.Wallace：“CD45 表面表达水平的改变影响胸腺选择的结果”（正在进行中）。

Kazuo Kawai: "Impaired Development of Vγ3 Dendritic Epidermal T Cells in p56^<lck> Protein Tyrosine Kinase-deficient and CD45 Protein Tyrosine Phosphatase-deficient Mice" Journal of Experimental Medicine. 181. 345-349 (1995)

Kazuo Kawai：“p56^<lck>蛋白酪氨酸激酶缺陷和 CD45 蛋白酪氨酸磷酸酶缺陷小鼠中 Vγ3 树突状表皮 T 细胞的发育受损”实验医学杂志 181. 345-349 (1995)。

Kong, Y.-Y., K.Kishihara, H.Yoshida et al.: "Generation of T cells with differential responses to alloantigens in CD45 exon 6-deficient mice" The Journal of Immunology. 154. 5725-5735 (1995)

Kong, Y.-Y., K.Kishihara, H.Yoshida 等人：“CD45 外显子 6 缺陷小鼠中对同种抗原具有不同反应的 T 细胞的生成”《免疫学杂志》。

Young-Yun Kong: "Generation of T Cells with Differential Responses in CD45 Exon 6-deficient Mice" (投稿中).

Young-Yun Kong：“在 CD45 外显子 6 缺陷小鼠中产生具有差异反应的 T 细胞”（进行中）。

Kong Y.-Y.,K.Kishihara,H.Yoshida,et al.: "Generation of T cells with differential responses to alloantigens in CD45 exon 6-deficient mice" The Journal of Immunology. 154. 5725-5735 (1995)

Kong Y.-Y.、K.Kishihara、H.Yoshida 等人：“CD45 外显子 6 缺陷小鼠中对同种抗原具有差异反应的 T 细胞的生成”免疫学杂志。