Role of Valpha24JalphaQ TCR T Cells in the Pathogenesis of Asthma

Valpha24JalphaQ TCR T 细胞在哮喘发病机制中的作用

• 批准号: 09670600
• 负责人: IWAMOTO Itsuo
• 金额: $ 2.18万
• 依托单位: Chiba University Scool of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670600/
• 关键词: Asthma; Valpha24JalphaQ TCR; NK T cells; IFN-gamma; Th2 cells; Th2タイプ免疫応答; TCR; 免疫制御

Atopic disorders are caused by disregulated activation of T helper 2 (Th2) cells that produce IL-4 and IL-5, Because the presence of IL-4 potently augments the differentiation of naive T cells into Th2 cells, it is important to seek the cell population which provides IL- 4 for naive T cells. Recently, a unique subpopulation of T cells, natural killer (NK) T cells, has been shown to produce a large amount of IL-4 upon activation, suggesting their regulatory role in initiation of Th2 cell differentiation. To determine whether NK T cells play a role in human Th2 diseases, we analyzed the NK T cells in patients with asthma and atopic dermatitis (AD). We performed a frequency analysis of the invariant Valpha24JalphaQ CD4^-CD8^- T cells, probable human NK T cells, and found that the NK T cells are significantly decreased in patients with asthma and AD.In addition, we found that the majority of human NK T cells from healthy subjects produce IFN-gamma but not IL-4 upon activation. Taken together, these results suggest that the decrease of NK T cells, which produce IFN-y, may be involved in the pathogenesis of atopic diseases, such as asthma and AD.

特应性疾病是由产生 IL-4 和 IL-5 的 T 辅助细胞 2 (Th2) 细胞活化失调引起的，因为 IL-4 的存在可有效增强初始 T 细胞向 Th2 细胞的分化，因此寻找为初始 T 细胞提供 IL-4 的细胞群。最近，一种独特的 T 细胞亚群，即自然杀伤 (NK) T 细胞，已被证明在激活后会产生大量 IL-4，表明它们在 Th2 细胞分化启动中的调节作用。为了确定 NK T 细胞是否在人类 Th2 疾病中发挥作用，我们分析了哮喘和特应性皮炎 (AD) 患者的 NK T 细胞。我们对不变的 Valpha24JalphaQ CD4^-CD8^- T 细胞（可能是人类 NK T 细胞）进行了频率分析，发现 NK T 细胞在哮喘和 AD 患者中显着减少。此外，我们发现大多数来自健康受试者的人类 NK T 细胞在激活后会产生 IFN-γ，但不会产生 IL-4。综上所述，这些结果表明，产生 IFN-γ 的 NK T 细胞的减少可能与哮喘和 AD 等特应性疾病的发病机制有关。

项目成果

Sakamoto A, et al: "Charactaristics of TCR Vα24JαQ T cells,a human counterpart for murine NKI^+ T cells, from normal subjects" J.Allergy Clin.Immunol. 102(印刷中). (1998)

Sakamoto A 等人：“来自正常受试者的 TCR Vα24JαQ T 细胞（鼠类 NKI+T 细胞的人类对应物）的特征”J. Allergy Clin 102（出版中）。

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Nakao A 等人：“高剂量口服耐受可防止抗原诱导的嗜酸性粒细胞募集到小鼠气道中。”

Nakao A,et al.: "High-dose oral tolerance prevents antigen-induced eosinophil recruitment into the mouse airways" Int.Immunol.10. 387-394 (1998)

Nakao A 等人：“高剂量口服耐受可防止抗原诱导的嗜酸性粒细胞募集到小鼠气道中”Int.Immunol.10。

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Nakao A, et al: "High-dose oral tolerance prevents antigen-induced eosinophil recruitment into the mouse airways" Int.Immunol.10. 387-394 (1998)

Nakao A 等人：“高剂量口服耐受可防止抗原诱导的嗜酸性粒细胞募集到小鼠气道中”Int.Immunol.10。