A basic study on immunotherapy of autoimmune male infertility with antigen-specific suppressor T cell factor (TsF)

抗原特异性抑制性T细胞因子（TsF）免疫治疗自身免疫性男性不育症的基础研究

• 批准号: 62570728
• 负责人: HOJO Kenji
• 金额: $ 1.54万
• 依托单位: Kagawa Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570728/
• 关键词: Therapy for infertility; Suppressor T cell line; Suppressor T cell factor; Effector T cell line; Experimental autoimmune orchitis; Antisperm immunity; サプレッサ-細胞株; エフェクターT細胞株; サブレッサーT細胞株; 男性不妊; サプレッサーT細胞因子; サプレッサーT細胞; 免疫調節

Experimental autoimmune orchitis (EAO) has proved to be a useful model for investigating the immunopathogenesis of male infertility and immunoregulatory mechanisms of this disease.There has been little or no evidence of effective therapy for autoimmune male infertility. Past ten years, our studies on the immunoregulation in guinea pig EAO have demonstrated the generation of suppressor T cells or their factors responsible for suppressing EAO induction and interfering with local adoptive transfer of EAO using antigen-specific effector T cells. Treatment of murine EAO with suppressor T cell factor (TsF) offers an especially attractive model to develop and validate a novel and specific immunotherapy for autoimmune male infertility. Results obtained from our project during the past 3 years are as follows:1. Suppressor T cells (Lyt-2^+) capable of inhibiting the EAO induction were induced in C3H/He mice by five doses of soluble (aggregate-free) testicular antigen intravenously.2. A suppresso … More r T cell line was derived through in vitro cultivation of spleen cells from C3H/He mice that were rendered hyperimmune by repeated subcutaneous injections with syngeneic testicular cells. This lined cells had the L3T4^+ phenotype and the capability of suppressing on-going EAO.3. Murine EAO with very high incidence could be developed in C3H/He mice by administering two or three subcutaneous injections of syngeneic testicular germ cells (TC) alone without resorting to adjuvant or cyclophosphamide. This model provides a very useful method for estimation of EAO-suppressing activity of TsF.4. An effector T cell line (L3T4^+) having the capability of transferring EAO systematically into naive recipients was established in BALB/c mice. This cell line is valuable for study on immunoregulation at the effector stage of EAO.5. Accurate and reproducible ELISA assay for detecting autoantibodies against sperm or TC in mice was developed.Thus, although the results from the present studies from our laboratory do not as yet isolate TsF molecules secreted or extracted from monocloned suppressor T cells or suppressor T cell hybridomas, preparations for investigating the TsF (e.g. TsF-secreting cells and assay systems for TsF activity) are making smooth progress. The isolation of a cDNA clone that may specify a polypeptide chain for the suppressor function is an attractive and obligatory subject. Less

实验性自身免疫性睾丸炎（EAO）已被证明是研究男性不育症的免疫发病机制和免疫调节机制的有用模型。过去十年，我们对自身免疫性男性不育症的有效治疗证据很少或没有。豚鼠 EAO 的免疫调节已证明抑制性 T 细胞或其因子的产生，负责抑制 EAO 诱导并使用抗原特异性效应 T 细胞干扰 EAO 的局部过继转移。用抑制性 T 细胞因子 (TsF) 治疗小鼠 EAO 提供了一个特别有吸引力的模型，用于开发和验证针对自身免疫性男性不育症的新型特异性免疫疗法。我们的项目在过去 3 年中获得的结果如下：1。通过静脉注射五剂可溶性（无聚集）睾丸抗原在 C3H/He 小鼠中诱导能够抑制 EAO 诱导的 (Lyt-2^+)。2。 T 细胞系是通过体外培养 C3H/He 小鼠的脾细胞而获得的，这些细胞通过重复皮下注射同源睾丸细胞而获得超免疫，该细胞系具有 L3T4^+ 表型和抑制正在进行的 EAO 的能力。3通过单独皮下注射两次或三次同源睾丸生殖细胞 (TC)，无需借助佐剂或药物，C3H/He 小鼠中发生发病率非常高的小鼠 EAO。该模型为评估 TsF.4 的 EAO 抑制活性提供了一种非常有用的方法，在 BALB/c 小鼠中建立了具有系统性地将 EAO 转移至初始受体的能力的效应 T 细胞系 (L3T4^+)。线对于EAO效应阶段的免疫调节研究具有重要价值。5.用于检测小鼠精子或TC自身抗体的准确且可重复的ELISA测定。因此，尽管我们实验室目前的研究结果尚未分离出从单克隆抑制性 T 细胞或抑制性 T 细胞杂交瘤中分泌或提取的 TsF 分子，但用于研究 TsF 的制剂（例如 TsF 分泌细胞和检测系统） TsF 活性）正在顺利分离可指定抑制功能的多肽链的 cDNA 克隆，这是一个有吸引力且强制性的课题。

项目成果

平峯千春: 炎症. 6. 279-283 (1986)

平岭千春：炎症。6. 279-283 (1986)

北条憲二: "自己免疫性精巣障害における免疫学的調節" 西日本泌尿器科. 51. 1411-1430 (1989)

Kenji Hojo：“自身免疫性睾丸疾病的免疫调节”West Japan Urology 51. 1411-1430 (1989)。

Masahiro Itoh: "Experimental autoimmune orchitis in C3H/He mice.A new and simple model with out resorting to adjuvant or the other immunopotentiating manipulations." Japan Society for Basic Reproductive Immunology Proceedings of the 4th Annual Meeting.

Masahiro Itoh：“C3H/He 小鼠实验性自身免疫性睾丸炎。一种新的简单模型，无需求助于佐剂或其他免疫增强操作。”

Masahiro Itoh: "Experimental autoimmune orchitis in C3H/He mice.A new and simple model without resorting to adjuvant or the other immunopotentiating manipulations." Japan Society for Basic Reproductive Immunology Proceedings of the 4th Annual Meeting.

Masahiro Itoh：“C3H/He 小鼠实验性自身免疫性睾丸炎。一种新的简单模型，无需求助于佐剂或其他免疫增强操作。”

Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state.

CD25 CD4 天然无反应性和抑制性 T 细胞维持的免疫自我耐受：通过打破其无反应性/抑制状态诱导自身免疫性疾病。

• DOI: 10.1093/intimm/10.12.1969
• 发表时间: 1998-12-01
• 期刊: International immunology
• 影响因子: 4.4
• 作者: Takeshi Takahashi;Y. Kuniyasu;M. Toda;N. Sakaguchi;M. Itoh;M. Iwata;J. Shimizu;S. Sakaguchi
• 通讯作者: S. Sakaguchi