Studies on Iuduction of Autologous MLR in the Autoimmune Diseases and its Pathological Roles.

自体MLR在自身免疫性疾病中的诱导及其病理作用的研究。

• 批准号: 01480186
• 负责人: KUMAGAI Katsuo
• 金额: $ 0.83万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01480186/
• 关键词: Autologous MLR; DR-antigen; helper T cells; gammadeltaT cells; lupus mouse; autoimmune disease; γδT細胞; サイトカイン; αβT細胞; MHC-クラスII抗原; 自己免疫疾患

On the specific nature and its biological significance of autologous mixed lymphocyte reaction (MLR), the following results are obtained. (1) Treatment with neuraminidase of the mixtures of stimulator cells and responder lymphocytes results in a marked enhancement of DNA replication in the autologous MLR. (2) Using this method, we are able to demonstrate that the autologous MLR is a helper T (TH) activation induced by DR antigens on accessory (AC) cells, of which the DNA replication is IL-2-independent, but dependent upon the multiple cytokines, IL-3, IL-5, IL-6 and IL-7. (3) The autologous MLR is also found to induce the generation of activated CD4^+ helper T cells, and also CD4^-CD8^- double negative (DN) T cells with a phenotype of alphabetaT cell receptor (alphabetaTcR)^+ or gammadeltaTcR^+. (4) Based on the findings of the specific nature of autologous MLR, the lymphoproliferation. Induced in the lymphoid tissues of MRL/lpr mouse is analyzed. As a result, it is found that abnormal proliferation of CD3^+CD4^-CD8^-B220^+ alphabetaTcR^+T cells in the lymphoid tissues may be a phenomenon in which precursors for this population can be proliferated in response to autologous accessory cells, mediated through certain antigens on the surface.

本文就自体混合淋巴细胞反应的特异性及其生物学意义作了如下讨论。(1)用神经氨酸酶处理刺激细胞和应答淋巴细胞的混合物导致自体MLR中DNA复制的显著增强。(2)使用这种方法，我们能够证明，自体MLR是辅助性T（TH）激活的DR抗原的辅助（AC）细胞，其中的DNA复制是IL-2的非依赖性，但依赖于多种细胞因子，IL-3，IL-5，IL-6和IL-7。(3)还发现自体MLR可诱导活化的CD 4 ^+辅助性T细胞的产生，以及具有γ-T细胞受体（γ-TcR）^+或γ-δ-TcR ^+表型的CD 4 ^-CD 8 ^-双阴性（DN）T细胞的产生。(4)基于自体MLR的特异性性质的研究结果，淋巴细胞增殖。分析了MRL/lpr小鼠淋巴组织中诱导的。结果发现，淋巴组织中的CD 3 ^+ CD 4 ^-CD 8 ^-B220^+ CD 4 TcR ^+T细胞的异常增殖可能是这样一种现象，即该群体的前体细胞可以通过表面上的某些抗原介导，响应于自体辅助细胞而增殖。

项目成果

SHUHJI SEKI: "Identification of activated T cell receptor gamma delta lymphocytes in the liver of tumorーbearing hosts." J.Clin.Invest.86. 409-415 (1990)

SHUHJI SEKI：“荷瘤宿主肝脏中活化 T 细胞受体 γ δ 淋巴细胞的鉴定。”J.Clin.Invest.86 (1990)。

MASATO KATO: "Responses of pokeweed mitogenーstimulated peripheral mononuclear cells to human recombinant interleukins 3 and 4." Lymphokine Res.9. 247-255 (1990)

加藤正人：“美洲商陆促细胞分裂原刺激的外周单核细胞对人重组白细胞介素 3 和 4 的反应。” 247-255 (1990)。

Kumagai,K.: "Production of interleukin 1 inhibitors by the murine macrophage cell line P388D_1 which produces interleukin 1" Immunol.Microbiol.33. 43-57 (1989)

Kumagai,K.：“产生白细胞介素 1 的鼠巨噬细胞系 P388D_1 产生白细胞介素 1 抑制剂”Immunol.Microbiol.33。

Ohteki, T., Seki, S., Abo, T., and Kumagai, K.: "Liver is a possible site for the proliferation of abnormal CD3^+4^-8^- double-negative lymphocytes in autoimmune MRL-lpr/lpr mice." J. Exd. Med.172. 7-12 (1990)

Ohteki, T.、Seki, S.、Abo, T. 和 Kumagai, K.：“肝脏是自身免疫 MRL-lpr/ 中异常 CD3^ 4^-8^- 双阴性淋巴细胞增殖的可能部位

Kumagai,K.: "Polyclonal activation of human lymphocytes by streptococcal preparations.Evidence for interlekin 2-independent generation of “double negative (CD3^+CD4^-CD8^-TcRγ/δ^+)"T.cells." J.Immunol.(1990)

Kumagai, K.：“链球菌制剂对人类淋巴细胞的多克隆激活。“双阴性 (CD3^+CD4^-CD8^-TcRγ/δ^+)”T 细胞独立于 interlekin 2 生成的证据。”免疫学（1990）