Splitter G A, Everlith K M
Department of Veterinary Science, University of Wisconsin-Madison 53706.
Infect Immun. 1989 Apr;57(4):1151-7. doi: 10.1128/iai.57.4.1151-1157.1989.
T-cell activation is dependent on nominal antigen associated with major histocompatibility complex (MHC) class II molecules and interleukin-1 (IL-1), both provided by antigen-presenting cells. We have studied the effects of Brucella abortus and recombinant bovine gamma interferon (IFN-gamma) on bovine macrophage expression of MHC class II and IL-1 molecules and subsequent T-cell proliferation in response to B. abortus. When peripheral blood mononuclear cells were cocultured with B. abortus and IFN-gamma, increasing amounts of IFN-gamma, from 1 to 100 U/ml, down regulated T-cell proliferation. Expression of MHC class II molecules on macrophages was increased independently by IFN-gamma or B. abortus treatment. Thus, class II molecule expression was not the cause of down regulation of T-cell proliferation as observed in other systems. However, B. abortus-IFN-gamma-treated macrophages obtained from overnight cultures had minimal membrane IL-1 compared with macrophages treated with B. abortus alone. Loss of membrane IL-1 required IFN-gamma and the o-polysaccharide of the lipopolysaccharide. IFN-gamma at 1 U/ml in combination with B. abortus produced a 32% decrease in T-cell response, while IFN-gamma at 100 U/ml added to B. abortus-treated cultures produced an 82% reduction in T-cell response. Membrane IL-1 levels were not altered when recombinant bovine IFN-alpha or the rough strain 45/20 of B. abortus, which lacks the o-polysaccharide, was used. Secreted IL-1 levels were unaffected by IFN-gamma and B. abortus treatment. The addition of recombinant bovine IL-1 beta (0.001 to 0.1 ng/ml) to B. abortus- and IFN-gamma-treated cultures failed to provide a signal necessary for T-cell proliferation. These data suggest that membrane IL-1 has a key role in T-cell activation in response to B. abortus. When the o-polysaccharide of B. abortus lipopolysaccharide is combined with IFN-gamma at an inappropriate time during an immune response, T-cell proliferation is prevented and cannot be restored by the addition of exogenous IL-1.
T细胞的激活依赖于与主要组织相容性复合体（MHC）II类分子相关的特异性抗原以及白细胞介素-1（IL-1），这两者均由抗原呈递细胞提供。我们研究了流产布鲁氏菌和重组牛γ干扰素（IFN-γ）对牛巨噬细胞MHC II类分子和IL-1分子表达的影响，以及随后T细胞对流产布鲁氏菌的增殖反应。当外周血单个核细胞与流产布鲁氏菌和IFN-γ共培养时，从1到100 U/ml增加剂量的IFN-γ会下调T细胞增殖。IFN-γ或流产布鲁氏菌处理均可独立增加巨噬细胞上MHC II类分子的表达。因此，II类分子的表达并非如在其他系统中所观察到的那样是T细胞增殖下调的原因。然而，与仅用流产布鲁氏菌处理的巨噬细胞相比，从过夜培养物中获得的经流产布鲁氏菌 - IFN-γ处理的巨噬细胞膜IL-1含量极少。膜IL-1的缺失需要IFN-γ和脂多糖的O-多糖。1 U/ml的IFN-γ与流产布鲁氏菌联合使用会使T细胞反应降低32%，而在经流产布鲁氏菌处理的培养物中加入100 U/ml的IFN-γ会使T细胞反应降低82%。当使用重组牛IFN-α或缺乏O-多糖的流产布鲁氏菌粗糙菌株45/20时，膜IL-1水平未发生改变。分泌的IL-1水平不受IFN-γ和流产布鲁氏菌处理的影响。向经流产布鲁氏菌和IFN-γ处理的培养物中添加重组牛IL-1β（0.001至0.1 ng/ml）未能提供T细胞增殖所需的信号。这些数据表明，膜IL-1在T细胞对流产布鲁氏菌的激活反应中起关键作用。当流产布鲁氏菌脂多糖的O-多糖在免疫反应的不适当时间与IFN-γ结合时，T细胞增殖会受到抑制，并且添加外源性IL-1无法恢复这种抑制。
