Early-onset multifocal inflammation in the transforming growth factor beta 1-null mouse is lymphocyte mediated
Early-onset multifocal inflammation in the transforming growth factor beta 1-null mouse is lymphocyte mediated
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DOI：
10.1073/pnas.92.26.12215
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发表时间：
1995-12-19
影响因子：
11.1
通讯作者：
Doetschman, T
中科院分区：
文献类型：
--
作者：
Diebold, RJ;Eis, MJ;Doetschman, T
转化生长因子β 1（TGF β 1）缺失小鼠死于早发性多灶性炎症性疾病引起的并发症。我们发现心肌细胞过度增殖，细胞间粘附分子1（ICAM-1）升高。为了确定哪些表型主要是由继发于炎症的TGF β 1缺乏引起的，我们应用免疫抑制疗法和与严重联合免疫缺陷（SCID）突变的遗传组合来抑制炎症反应。用白细胞功能相关抗原1的抗体治疗可以使寿命延长一倍，减少炎症，并延迟心脏细胞增殖。无TGF β 1基因的SCID小鼠没有表现出炎症或心脏细胞增殖，存活至成年，并表现出正常的主要组织相容性复合体II（MHC II）和ICAM-1水平。由TGF β 1缺失的SCID母亲所生的TGF β 1缺失的幼崽没有表现出明显的先天性心脏缺陷，这表明TGF β 1单独在心脏发育中不起重要作用。这些结果表明，淋巴细胞对于炎症反应、心肌细胞增殖以及MHC II和ICAM-1表达升高是必不可少的，揭示了TGF β 1的重要作用。调节淋巴细胞增殖和活化，有助于维持自身耐受。
Transforming growth factor beta 1 (TGF beta 1)-null mice die from complications due to an early-onset multifocal inflammatory disorder. We show here that cardiac cells are hyperproliferative and that intercellular adhesion molecule 1 (ICAM-1) is elevated. To determine which phenotypes are primarily caused by a deficiency in TGF beta 1 from those that are secondary to inflammation, we applied immunosuppressive therapy and genetic combination with the severe combined immunodeficiency (SCID) mutation to inhibit the inflammatory response. Treatment with antibodies to the leukocyte function-associated antigen 1 doubled longevity, reduced inflammation, and delayed heart cell proliferation. TGF beta 1-null SCID mice displayed no inflammation or cardiac cell proliferation, survived to adulthood, and exhibited normal major histocompatibility complex II (MHC II) and ICAM-1 levels. TGF beta 1-null pups born to a TGF beta 1-null SCID mother presented no gross congenital heart defects, indicating that TGF beta 1 alone does not play an essential role in heart development. These results indicate that lymphocytes are essential for the inflammatory response, cardiac cell proliferation, and elevated MHC II and ICAM-1 expression, revealing a vital role for TGF beta 1. in regulating lymphocyte proliferation and activation, which contribute to the maintenance of self tolerance.