Contractor N V, Bassiri H, Reya T, Park A Y, Baumgart D C, Wasik M A, Emerson S G, Carding S R
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia 19104-6076, USA.
J Immunol. 1998 Jan 1;160(1):385-94.
IL-2-deficient (IL-2(-/-)) mice develop disorders of the hemopoietic and immune systems characterized by anemia, lymphocytic hyperplasia, and colitis. The mechanisms responsible for these abnormalities remain unclear. To investigate the underlying basis of autoimmunity, the particular role of commensal gut flora in the initiation of colitis, and the role of IL-2 in the development of intestinal intraepithelial lymphocytes (iIEL), we evaluated IL-2(-/-) mice reared and maintained under gnotobiotic (germfree) conditions. By 8 wk of age, 80% (20 of 25) of germfree IL-2(-/-) mice show signs of disease, including anemia, disturbances in bone marrow hemopoietic cells, lymphocytic hyperplasia, and generalized autoimmunity, similar to those seen in specific pathogen-free (SPF) IL-2(-/-) mice. In striking contrast to SPF IL-2(-/-) mice, germfree IL-2(-/-) mice do not develop colitis. However, the numbers of gammadelta+ and TCR alphabeta+ CD8 alphaalpha+ iIELs are reduced, and in lethally irradiated SPF IL-2(+/+) mice, reconstituted with IL-2(-/-) bone marrow TCR gammadelta+ iIELs fail to develop, consistent with an important role of IL-2/IL-2R signaling in the development of gammadelta iIELs. Consequently, our findings demonstrate that the colitis seen in SPF IL-2(-/-) mice depends upon the presence of intestinal bacterial flora and that environmental Ags are not responsible for the anemia and extraintestinal lymphoid hyperplasia that occur in IL-2(-/-) mice. Thus, germfree IL-2(-/-) mice represent a unique system in which the role of IL-2 deficiency in hemopoietic and immune system disorders can be investigated in dissociation from complications that may arise due to colitis.
白细胞介素-2缺陷（IL-2(-/-)）小鼠会出现造血和免疫系统紊乱，其特征为贫血、淋巴细胞增生和结肠炎。导致这些异常的机制尚不清楚。为了研究自身免疫的潜在基础、共生肠道菌群在结肠炎发病中的特殊作用以及白细胞介素-2在肠道上皮内淋巴细胞（iIEL）发育中的作用，我们评估了在悉生（无菌）条件下饲养和维持的IL-2(-/-)小鼠。到8周龄时，80%（25只中的20只）无菌IL-2(-/-)小鼠出现疾病迹象，包括贫血、骨髓造血细胞紊乱、淋巴细胞增生和全身性自身免疫，与无特定病原体（SPF）的IL-2(-/-)小鼠所见相似。与SPF IL-2(-/-)小鼠形成鲜明对比的是，无菌IL-2(-/-)小鼠不会发生结肠炎。然而，γδ+和TCRαβ+ CD8αα+ iIEL的数量减少，并且在用IL-2(-/-)骨髓重建的经致死性照射的SPF IL-2(+/+)小鼠中，TCRγδ+ iIEL无法发育，这与IL-2/IL-2R信号在γδ iIEL发育中的重要作用一致。因此，我们的研究结果表明，SPF IL-2(-/-)小鼠中所见的结肠炎取决于肠道细菌菌群的存在，并且环境抗原并非导致IL-2(-/-)小鼠贫血和肠外淋巴样增生的原因。因此，无菌IL-2(-/-)小鼠代表了一个独特的系统，在其中可以独立于因结肠炎可能出现的并发症来研究IL-2缺乏在造血和免疫系统紊乱中的作用。
