Lack of apoptosis of infiltrating cells as the mechanism of high susceptibility to EAE in DA rats.
Lack of apoptosis of infiltrating cells as the mechanism of high susceptibility to EAE in DA rats.
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缺乏浸润细胞的凋亡是对DA大鼠EAE敏感性高的机制。
DOI：
10.1155/2001/32636
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Shahin, A
中科院分区：
文献类型：
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作者：
Lukic, M L;Mensah-Brown, E;Galadari, S;Shahin, A
黑鼠（DA）极易诱发th -l介导的自身免疫性疾病，包括实验性变应性脑脊髓炎（EAE）。与其他仅用在完全弗氏佐剂（CFA）中乳化的脑原诱导疾病的易感大鼠菌株相反，DA大鼠在注射不完全弗氏佐剂（IFA）或Titermax（假定为Th-2定向佐剂）中的脑原后发生EAE。免疫DA大鼠的淋巴结细胞在体外刺激下产生的干扰素-γ (IFN-γ)明显高于耐药的Oxford （AO）大鼠。然而，来自这两种菌株的细胞产生大量的IL-10而不产生IL-4。来自EAE易感（AO × DA）大鼠的免疫淋巴结细胞在亚致死辐照的亲代DA中诱导临床症状，而AO大鼠则没有。这些受体靶组织的病理组织学清楚地表明，两个亲本株均有单核细胞浸润。然而，在被动转移8天后，DA大鼠的CD4+细胞数量明显增加，凋亡细胞数量明显减少。我们推测，除了IFN-γ和TNF-α的产生增加外，由于TGF-β缺乏下调，靶组织中入侵细胞对早期凋亡的抵抗可能导致DA大鼠对EAE异常易感性。
Dark Agouti (DA) rats are highly susceptible to induction of Th-l-mediated autoimmunity disease, including experimental allergic encephalomyelitis (EAE). In contrast to other susceptible rat strains in which disease is induced only with encephalitogen emulsified in complete Freund's adjuvants (CFA), in DA rats EAE develops after injection of encephalitogen in incomplete Freund's adjuvants (IFA) or Titermax, putative Th-2 directed adjuvant. Lymph node cells derived from immunized DA rats and stimulated in vitro produce significantly more Interferon-γ (IFN-γ) than resistant Albino Oxford (AO) rats. However, cells derived from both strains produce large amounts of IL-10 but not IL-4. Immunized lymph node cells derived from EAE susceptible (AO × DA) F1rats induce clinical signs of disease in sublethally irradiated parental DA but not AO rats. The pathohistology of the target tissue in these recipients clearly demonstrated infiltration of mononuclear cells in both parental strains. However, the number of CD4+ cells was significantly higher and number of apoptotic cells significantly lower in DA rats sacrificed 8 days after passive transfer. We postulate that in addition to higher IFN-γ and TNF-α production, resistance to early apoptosis of the invading cells in the target tissue possibly due to lack of downregulation by TGF-β leads to exceptional susceptibility to EAE in DA rats.