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克隆的自身Ia反应性T细胞在同基因小鼠皮肤中引发扁平苔藓样病变。

Cloned auto-Ia-reactive T cells elicit lichen planus-like lesion in the skin of syngeneic mice.

作者信息

Saito K, Tamura A, Narimatsu H, Tadakuma T, Nagashima M

出版信息

J Immunol. 1986 Oct 15;137(8):2485-95.

PMID:2944957
Abstract

To explore the physiologic or pathologic roles of autoreactive T cells, we examined immunological functions of several autoreactive mouse T cell clones in vitro and in vivo. All of the T cell clones were Lyt-2-, L3T4+ and showed self-I region-restricted proliferative responses (one clone was self-I-E restricted, the other clones were self-I-A restricted). One clone derived from C57BL/6 mouse and reactive to the self-I-Ab product (clone bb1-2) showed cross-reactivity to the I-Ak product. Among four such auto-Ia-reactive T cell clones examined, one clone produced fairly large amounts of interleukin 2 (IL 2) in response to syngeneic stimulator cells, and mediated help for the in vitro cytotoxic T cell (CTL) responses of syngeneic thymocytes, whereas this clone did not mediate in vitro antibody responses of syngeneic B cells. The other three clones were producers of small amounts of IL 2 and did not mediate the in vitro CTL responses. Among the three clones, clone bb1-2 showed strong regulatory function, and clone kk-1 (B10.BR origin and self-I-Ak reactive) showed weak regulatory function in vitro antibody responses of syngeneic B cells. The physiologic or pathologic roles of autoreactive T cells in vivo were explored by injecting subcutaneously clone kk-1 T cells or clone bb1-2 T cells into the footpads of the respective syngeneic mice. Clone kk-1 T cells injected into syngeneic mice elicited swelling of the footpad and marked accumulation of mononuclear cells in the dermis, leaving the epidermis intact, as in the delayed-type hypersensitivity reaction. As a notable finding, clone bb1-2 T cells injected into syngeneic mice elicited marked swelling of the footpad and lichen planus-like skin lesions, i.e., infiltration of lymphocytes in the epidermis and epidermal cell damage. The lymphocytes infiltrating in the epidermis were evaluated, as were the injected clone bb1-2 T cells expressing the Lyt-1.2 phenotype, by examination of the skin lesions elicited in C3H/He mice (H-2k, Lyt-1.1, 2.1) by the clone T cells. Clone bb1-2 T cells exerted in vitro cytotoxicity against H-2b and H-2k target cells, whereas clone kk-1 T cells did not show any cytotoxic activity, indicating a correlation between the cytotoxic activity of clone bb1-2 T cells and their ability to elicit lichen planus-like lesions.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

为了探究自身反应性T细胞的生理或病理作用,我们在体外和体内检测了几种自身反应性小鼠T细胞克隆的免疫功能。所有T细胞克隆均为Lyt-2阴性、L3T4阳性,并表现出自身I区限制性增殖反应(一个克隆为自身I-E限制性,其他克隆为自身I-A限制性)。一个源自C57BL/6小鼠且对自身I-Ab产物有反应的克隆(克隆bb1-2)对I-Ak产物表现出交叉反应性。在所检测的四个此类自身Ia反应性T细胞克隆中,一个克隆在同基因刺激细胞存在时产生相当大量的白细胞介素2(IL-2),并介导同基因胸腺细胞体外细胞毒性T细胞(CTL)反应的辅助作用,而该克隆不介导同基因B细胞的体外抗体反应。其他三个克隆产生少量IL-2,且不介导体外CTL反应。在这三个克隆中,克隆bb1-2表现出强大的调节功能,克隆kk-1(源自B10.BR且对自身I-Ak有反应)在同基因B细胞的体外抗体反应中表现出较弱的调节功能。通过将克隆kk-1 T细胞或克隆bb1-2 T细胞皮下注射到各自同基因小鼠的足垫中,探究了体内自身反应性T细胞的生理或病理作用。注射到同基因小鼠体内的克隆kk-1 T细胞引发足垫肿胀以及真皮中单核细胞的显著积聚,表皮保持完整,如同迟发型超敏反应。一个值得注意的发现是,注射到同基因小鼠体内的克隆bb1-2 T细胞引发足垫显著肿胀和扁平苔藓样皮肤病变,即淋巴细胞浸润到表皮以及表皮细胞损伤。通过检查克隆T细胞在C3H/He小鼠(H-2k,Lyt-1.1,2.1)中引发的皮肤病变,评估了浸润到表皮中的淋巴细胞以及表达Lyt-1.2表型的注射克隆bb1-2 T细胞。克隆bb1-2 T细胞对H-2b和H-2k靶细胞具有体外细胞毒性,而克隆kk-1 T细胞未表现出任何细胞毒性活性,表明克隆bb1-2 T细胞的细胞毒性活性与其引发扁平苔藓样病变的能力之间存在相关性。(摘要截取自400字)

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