Cutting edge:: IFN-γ regulates the induction and expansion of IL-17-producing CD4 T cells during mycobacterial infection
Cutting edge:: IFN-γ regulates the induction and expansion of IL-17-producing CD4 T cells during mycobacterial infection
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DOI：
10.4049/jimmunol.177.3.1416
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发表时间：
2006-08-01
影响因子：
4.4
通讯作者：
Castro, Antonio G.
中科院分区：
文献类型：
--
作者：
Cruz, Andrea;Khader, Shabaana A.;Castro, Antonio G.
T 细胞反应对于控制感染很重要，但如果不加以调节，就会有害。感染分枝杆菌的 IFN-γ 缺陷小鼠表现出肉芽肿病变内活化效应 T 细胞和中性粒细胞的积累增加。这些细胞不能控制细菌生长并损害受感染组织的完整性。我们发现，IFN-γ缺陷小鼠在感染牛分枝杆菌卡介苗后，产生 IL-17 的 T 细胞数量增加。此外，外源性IFN-γ增加卡介苗感染的骨髓源性树突细胞产生的IL-12并减少IL-23的产生，并降低由这些骨髓源性树突细胞诱导的产生IL-17的T细胞的频率。这些数据支持这样的假设：在分枝杆菌感染期间，产生 IFN-γ 和 IL-17 的 T 细胞都被诱导，但 IFN-γ 起到限制产生 IL-17 的 T 细胞群体的作用。这种反调节途径可能是限制分枝杆菌相关免疫介导病理学的重要因素。
T cell responses are important to the control of infection but are deleterious if not regulated. IFN-gamma-deficient mice infected with mycobacteria exhibit enhanced accumulation of activated effector T cells and neutrophils within granulomatous lesions. These cells do not control bacterial growth and compromise the integrity of the infected tissue. We show that IFN-gamma-deficient mice have increased numbers of IL-17-producing T cells following infection with Mycobacterium bovis bacille Calmette Guerin. Furthermore, exogenous IFN-gamma increases IL-12 and decreases IL-23 production by bacille Calmette Guerin-infected bone marrow-derived dendritic cells and reduces the frequency of IL-17-producing T cells induced by these bone marrow-derived dendritic cells. These data support the hypothesis that, during mycobacterial infection, both IFN-gamma- and IL-17-producing T cells are induced, but that IFN-gamma serves to limit the IL-17-producing T cell population. This counterregulation pathway may be an important factor in limiting mycobacterially associated immune-mediated pathology.