Autoimmunity associated with TGF-beta 1-deficiency in mice is dependent on MHC class II antigen expression
Autoimmunity associated with TGF-beta 1-deficiency in mice is dependent on MHC class II antigen expression
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DOI：
10.1172/jci119017
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发表时间：
1996-11-01
影响因子：
15.9
通讯作者：
Roberts, AB
中科院分区：
文献类型：
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作者：
Letterio, JJ;Geiser, AG;Roberts, AB
在转化生长因子β1缺陷小鼠中发现的进行性炎症过程与自身免疫的几种表现有关，包括循环中的核抗原抗体，免疫复合体沉积，以及I类和II类主要组织相容性复合体(MHC)抗原的表达增加。通过将转化生长因子-β1缺失[转化生长因子-β1((-/-))]基因型与转化生长因子-β1缺失[MHC-II(-/-)]杂交，确定了MHC-II类抗原在该表型发生中的作用。背景：小鼠同时具有转化生长因子-β1缺失等位基因和转化生长因子-β1(-/-)纯合子；MHC-II(-/-)]小鼠没有炎性浸润、循环自身抗体或肾小球免疫复合物沉积的证据，相反，这些动物表现出广泛的髓外造血，并伴有进行性脾肿大和腺病，仅比转化生长因子-β1((-/-))；MHC-II(+/+)小鼠存活时间略长。在MHC II类缺陷小鼠中也没有CD4(+)T细胞的作用，通过在II类阳性的转化生长因子-β1((-/-))小鼠中注射抗CD4单抗直接证明了这一作用。观察到的炎症减轻和存活率的提高强调了CD4(+)细胞在自身免疫过程的发病机制中的重要性，并表明转化生长因子-β1((-/-))；MHC-II(-/-)小鼠额外缺乏II类抗原可能是导致它们极端的髓样化生的原因之一。因此，MHC-II类抗原在转化生长因子-β1缺陷小鼠的自身免疫表达中是必不可少的，并且正常情况下可能与转化生长因子-β1协同调节造血。
The progressive inflammatory process found in transforming growth factor beta 1 (TGF-beta 1>-deficient mice is associated with several manifestations of autoimmunity, including circulating antibodies to nuclear antigens, immune complex deposition, and increased expression of both class I and class II major histocompatibility complex (MHC) antigens. The contribution of MHC class II antigens to the genesis of this phenotype has been determined by crossing the TGF-beta 1-null [TGF-beta 1((-/-))] genotype into the MHC class II-deficient [MHC-II(-/-)] background, Mice homozygous for both the TGF-beta 1 null allele and the class II null allele [TGF-beta 1((-/-));MHC-II(-/-)] are without evidence of inflammatory infiltrates, circulating autoantibodies, or glomerular immune complex deposits, Instead, these animals exhibit extensive extramedullary hematopoiesis with progressive splenomegaly and adenopathy, surviving only slightly longer than TGF-beta 1((-/-));MHC-II(+/+) mice. The role of CD4(+) T cells, which are also absent in MHC class II-deficient mice, is directly demonstrated through the administration of anti-CD4 monoclonal antibodies in class II-positive, TGF-beta 1((-/-)) mice. The observed reduction in inflammation and improved survival emphasize the significance of CD4(+) cells in the pathogenesis of the autoimmune process and suggest that the additional absence of class II antigens in TGF-beta 1((-/-));MHC-II(-/-) mice may contribute to their extreme myeloid metaplasia. Thus, MHC class II antigens are essential for the expression of autoimmunity in TGF-beta 1-deficient mice, and normally may cooperate with TGF-beta 1 to regulate hematopoiesis.