Studies on the Pathogenesis of Immune Disorders by the Analysis of the Differentiation and Regulation of the Lmyphocytes.

通过分析淋巴细胞的分化和调节来研究免疫性疾病的发病机制。

• 批准号: 63480234
• 负责人: YATA Junichi
• 金额: $ 4.16万
• 依托单位: Tokyo Medical and Dental 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: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-63480234/
• 关键词: Primary immunodeficiency; T cell differentiation; Regulation by NK cells; sigmadelta T cells; Allergen-specific B cells; Hashimot's thyroiditis; Anti-thyroglobulin antibody; キラ-細胞; インタ-ロイキン; γδ型T細胞; 抗原結合B細胞; 卵白アレルギ-; σδ型T細胞; 細胞傷害活性; T細胞レセプタ-

The lymphocytes from immune disorders were analyzed for their differentiation and the regulatin of their functions in order to disclose the pathogenesis. T cells can be divided into alphabeta type and sigmadelta type according to the peptides constituting the antigen receptor. The later T cells are less dependent on the thymus and seem to be more primitive. Sigmadelta T cells were increased in some of the immunodeficiency patients with T cell deficiency indicating compensations of ordinary T cells. However, part of the cytotoxic function of these sigmadelta T cells was impaired and their differentiation was suggested to be not complete. Bone marrow cells and later irradiated thymus were transplanted to a patient with T cell defect probab lly due to impaired development of lymphoid stem cells. NK cells was generated but T cells developed only after thymus transplantation. NK cells seemedo down-regulate the generation of granulocytes and T cells did that of NK cells, which suggested the … More presence of mutual regulation among granulocytes, NK cells and T cells. Thus appeared sigmadelta T cells responded well to interleukin (IL) -2 but alphadelta T cells did not. Allogeneic irradiated thymus might not be sufficient for the full differentiation of alphadelta T cells. It was suggested by a case with normal B cells and hypogammaglobulinemia that impaired differentiation of CD4^+T cells from CD45RA^+ to CD45RO^+ causes defective helper function. The number of ovalbumin (OVA) specific B cells was observed to increase gradually according to age and was more prominent in OVA-allergic patients. The increase of OVA-specific B cells preceded to the appearance of serum anti-OVA antibody. Enumulation of allergenspecific B cells may be valuable to predict food allevgy. In vitro study of antithyroglobulin antibody production from Hashimoto's thyroiditis revealed that B cells were fully activated in some patients and they were inactive for moment but showed potentiality to produce the antibody in other patients. Less

分析了免疫缺陷患者的淋巴细胞的分化和功能调节，以披露发病机理。根据构成抗原受体的肽，可以将T细胞分为字母类型和Sigmadelta类型。后来的T细胞较少依赖胸腺，并且似乎更原始。 T细胞缺乏症的一些免疫缺陷患者中，sigmadelta T细胞增加，表明普通T细胞的补偿。然而，这些sigmadelta T细胞的细胞毒性功能的一部分受损，并建议其分化不完整。将骨髓细胞和随后的胸腺辐照移植到患有T细胞缺陷的患者可能是由于淋巴样干细胞发育受损而导致的。生成NK细胞，但仅在胸腺移植后才出现T细胞。 NK细胞Seemedo下调了粒细胞和T细胞的产生，而NK细胞的产生表明，粒细胞，NK细胞和T细胞之间存在更多相互调控。这似乎对白介素（IL）-2的sigmadelta T细胞反应良好，但αT细胞没有。同种异体辐照的胸腺可能不足以完全分化αT细胞。它是由正常B细胞​​和低磁性血症的病例提出的，该病例损害了从CD45RA^+到CD45RO^+的CD4^+ T细胞分化会导致助手功能缺陷。观察到椭圆蛋白（OVA）特定B细胞的数量根据年龄逐渐增加，并且在OVA过敏患者中更为突出。 OVA特异性B细胞的增加，先于血清抗OVA抗体的出现。对过敏原B细胞的列举对于预测食物的细胞可能很有价值。体外研究对桥本甲状腺炎的抗肌球蛋白抗体产生的生产表明，某些患者的B细胞被完全激活，并且它们暂时不活跃，但在其他患者中表现出产生抗体的潜力。较少的

项目成果

Morio,T.,Takase,K.,Okawa,H.Oguchi,M.,Kanbara,M.,Hiruma,F.,Yoshino,K.,Kanko,T.Asamura,S.^<・・・> and Yata,J.: "The increase of nonーMHCーrestricted cytotoxic cells(γδーTCR bearing T cells or NK cells)and the abnormal differentiation of B cells in WiskottーAldric

Morio, T.、Takase, K.、Okawa, H. Oguchi, M.、Kanbara, M.、Hiruma, F.、Yoshino, K.、Kanko, T. Asamura, S. ^<...> 和 Yata ,J.：“Wiskott-Aldric 中非 MHC 限制性细胞毒性细胞（带有 γδ-TCR 的 T 细胞或 NK 细胞）的增加和 B 细胞的异常分化

Morio, T., Takase, K., Okawa, H., Oguchi, M., Kanbara, M., Hiruma, F., Yoshino, K., Kaneko, T., Asamura, S., Inoue, T., Tsuji, Y., Tasaka, H., Kakei, I., Miyata, K. and Yata, J. :"The increase of non-MHC-restricted cytotoxic cells (signd/delta-TCR bearing

森尾 T.、高濑 K.、大川 H.、大口 M.、神原 M.、昼间 F.、吉野 K.、金子 T.、浅村 S.、井上 T.、

Takagi,S.,Minaguchi,J.,Okawa,H.and Yata,J.: "Interferon-induced resistance of tumor target cells against lysis by interleukin activated killer cells." Tohoku Journal of Experimental Medicine. 157. 131-136 (1989)

Takagi,S.、Minaguchi,J.、Okawa,H. 和 Yata,J.：“干扰素诱导的肿瘤靶细胞对白细胞介素激活的杀伤细胞裂解的抵抗力。”

Morio,T.,Takase,K.,Okawa,H.,Oguchi,M.,Kanbara,M.,Hiruma,F.,Yoshino,K.and Yata,J.: "The increase of non-MHC-restricted cytotoxic cells(δ/σ TCR bearing T cells or NK cells)and abnormal differentiation of B cells in Wiskott-Aldrich syndrome." Clinical Immuno

Morio, T.、Takase, K.、Okawa, H.、Oguchi, M.、Kanbara, M.、Hiruma, F.、Yoshino, K. 和 Yata, J.：“非 MHC 限制性细胞毒性的增加“Wiskott-Aldrich 综合征中的细胞（带有 δ/σ TCR 的 T 细胞或 NK 细胞）和 B 细胞的异常分化。”

Morio, T., Nonoyama, S. and Yata, J. :"Suppression of in vitro immunoglobulin synthesis by CD16 (Leulla)^+CD56 (NKH1, Leu19)^+non-T lineage NK cells ; lack of suppression of cells from immunodeficient patients." Clin. exp. Immunol.78(1). 159, (1989)

Morio, T.、Nonoyama, S. 和 Yata, J.：“CD16 (Leulla)^ CD56 (NKH1、Leu19)^ 非 T 谱系 NK 细胞对体外免疫球蛋白合成的抑制；对免疫缺陷患者的细胞缺乏抑制