Maekawa Yoichi, Tsukumo Shin-Ichi, Okada Hiroko, Kishihara Kenji, Yasutomo Koji
Department of Immunology and Parasitology, School of Medicine, University of Tokushima, Tokushima, Japan.
Transplantation. 2003 Jul 27;76(2):415-20. doi: 10.1097/01.TP.0000078900.71840.2B.
Thymic deletion purges the repertoire of most developing T cells with the potential for overt self-reactivity, but some self-specific cells do emerge into the peripheral pool. Under most conditions, these potentially autoaggressive cells remain in a quiescent state. However, in some circumstances, they become activated and acquire effector function, leading to immune disease. It is thus important to clarify the mechanism(s) responsible for determining the balance between such inappropriate T-cell activation and the normal state of peripheral tolerance. In this article, we show that chronic elevation of interleukin-15 levels interferes with the tolerant state of CD8+ T cells through a process that involves activation of nonlymphoid antigen-presenting cells by CD4+asialo-GM1+ (ASGM1) or both CD4+ASGM1- and CD4-ASGM1+ cells. These findings suggest a potential role for dysregulated interleukin-15 production in promoting tolerance breakdown. This new information may be of potential use in improving tumor vaccines to self-antigens and in ameliorating autoimmune or graft-versus-host disease.
胸腺清除作用会清除大多数具有明显自身反应性潜能的发育中T细胞库，但仍有一些自身特异性细胞进入外周库。在大多数情况下，这些潜在的自身攻击性细胞保持静止状态。然而，在某些情况下，它们会被激活并获得效应功能，从而导致免疫疾病。因此，阐明决定这种不适当的T细胞激活与外周耐受正常状态之间平衡的机制非常重要。在本文中，我们表明白细胞介素-15水平的慢性升高通过一个涉及CD4⁺唾液酸缺乏神经节苷脂GM1⁺（ASGM1）或CD4⁺ASGM1⁻和CD4⁻ASGM1⁺细胞激活非淋巴细胞抗原呈递细胞的过程，干扰CD8⁺T细胞的耐受状态。这些发现表明白细胞介素-15产生失调在促进耐受破坏中可能发挥作用。这一新信息可能在改进针对自身抗原的肿瘤疫苗以及改善自身免疫性疾病或移植物抗宿主病方面具有潜在用途。
