T-CELLS IN INFLAMMATORY BOWEL-DISEASE - PROTECTIVE AND PATHOGENIC ROLES
T-CELLS IN INFLAMMATORY BOWEL-DISEASE - PROTECTIVE AND PATHOGENIC ROLES
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DOI：
10.1016/1074-7613(95)90086-1
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发表时间：
1995-08-01
期刊：
影响因子：
32.4
通讯作者：
POWRIE, F
中科院分区：
文献类型：
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作者：
POWRIE, F
免疫系统暴露于肠道中大量的抗原，包括来自食物和细菌的抗原，然而粘膜免疫应答的特征在于缺乏对这些抗原的细胞介导的免疫应答。事实上，口服暴露于抗原可导致随后对喂食抗原的全身低反应性状态（Weiner，1994），这表明存在适当的调节机制，其积极地防止对肠道中存在的抗原的免疫应答的发展。这些措施大致可分为三类。首先，具有T细胞亚群和T细胞选择改变的小鼠：T细胞受体-α（TCR α）链缺陷小鼠、TCR 6链缺陷小鼠和主要组织相容性复合体（MHC）II类基因缺陷小鼠（Mombaiden等人，1993）用CD 45 RBh + CD 4 + T细胞恢复的SCID小鼠（Morrissey等，1993; Powrie等人，1993，1994 a）、HLA-B27转基因大鼠（Hammer等，1990）和移植了正常F1骨髓细胞的人CD 3 ε转基因小鼠（霍兰德等人，1995年a）。第二，靶向破坏细胞因子基因的小鼠：白细胞介素-2（IL-2）（Sadlack等人，1993）IL-10（Kuhn等人，1993）和转化生长因子-51（TGF 61）缺陷小鼠（Shull等人，1992; Kulkarni等人，1993年）。第三，缺乏信号传导蛋白的小鼠; G蛋白亚基Ga 3缺陷小鼠（Rudolph等人，1995年）。虽然这些模型乍一看非常不同，但它们都涉及干扰免疫系统的操作。事实上，所有这些IBD模型都可能通过破坏T细胞依赖性调节系统的共同特征诱导疾病，该调节系统通常用于保护肠道免受细胞介导的免疫攻击。
The immune system is exposed to an enormous number of antigens in the intestine, including those derived from food and bacteria, yet mucosal immune responses are characterized by a lack of cell-mediated immune responsiveness to these antigens. Indeed, oral exposure to antigen can lead to a subsequent state of systemic hyporeactivity to the fed antigen (Weiner, 1994) suggesting that there are regulatory mechanisms in place that actively prevent development of immune responses to antigens present in the gut.In the last 2 years, an impressive number of different models of inflammatory bowel disease (IBD) in mice and rats have been described. These can broadly be divided into three groups. First, mice with alterations in T cell subpopulations and T cell selection: T cell receptor-a (TCRa) chain-deficient mice, TCR6 chain-deficient mice, and major histocompatibility complex (MHC) class II genedeficient mice (Mombaerts et al., 1993) SCID mice restored with CD45RBh’CD4’T cells (Morrissey et al., 1993; Powrie et al., 1993, 1994a), HLA-B27 transgenic rats (Hammer et al., 1990) and human CD3s transgenic mice, transplanted with normal Fl bone marrow cells (Hollander et al., 1995a). Second, mice with targeted disruption of cytokine genes: interleukin-2 (IL-2)(Sadlack et al., 1993) IL-10 (Kuhn et al., 1993) and transforming growth factor-51 (TGF61)-deficient mice (Shull et al., 1992; Kulkarni et al., 1993). Third, mice lacking signaling proteins; G protein subunit Ga3-deficient mice (Rudolph et al., 1995). While these models at first sight look very different, they all involve manipulations that perturb the immune system. Indeed, all of these models of IBD may induce disease by the common feature of disrupting a Tcell-dependent regulatory system that normally functions to protect the gut from cell-mediated immune attack.