Li Ming, O'Sullivan Kim M, Jones Lynelle K, Lo Cecilia, Semple Timothy, Kumanogoh Atsushi, Kikutani Hitoshi, Holdsworth Stephen R, Kitching Richard
Centre for Inflammatory Diseases, Monash University Department of Medicine, Clayton, Victoria, Australia.
Immunology. 2009 Sep;128(1):114-22. doi: 10.1111/j.1365-2567.2009.03098.x.
CD100 participates in adaptive immune responses and is important in neural cell migration. To determine the role of endogenous CD100 in severe glomerular inflammation, we induced experimental crescentic glomerulonephritis by planting a foreign antigen in glomeruli of sensitized normal and CD100-deficient (CD100(-/-)) mice. Fewer CD100(-/-) glomeruli exhibited crescent formation or severe histological changes. Antigen-specific immune responses were reduced in CD100(-/-) mice. There was less interferon (IFN)-gamma and interleukin (IL)-4 production by splenocytes and fewer activated T and B cells were present in lymph nodes of immunized CD100(-/-) mice. Serum antigen-specific immunoglobulin (IgG) levels were also decreased. Glomerular macrophage and CD4(+) cell infiltration, and IgG and C3 deposition were attenuated. Normal kidneys expressed mRNA for CD100 and plexin-B1 (the tissue receptor of CD100). Direct immunofluorescence showed that renal-CD100 protein was predominantly in tubules, while plexin-B1 was present in both glomeruli and tubules. To determine whether glomerular plexin-B1 mediates leucocyte recruitment via leucocyte CD100, recruitment was studied after passive transfer of heterologous antibody (attracting neutrophils) or isologous antibody (attracting macrophages). Glomerular macrophages were reduced in CD100(-/-) mice, but neutrophil recruitment was equivalent, consistent with CD100 expression on macrophages, but not neutrophils. CD100 promotes severe nephritogenic immune responses and leucocyte CD100-glomerular plexin-B1 interactions enhance macrophage recruitment to glomeruli.
CD100参与适应性免疫反应，在神经细胞迁移中起重要作用。为了确定内源性CD100在严重肾小球炎症中的作用，我们通过将外源抗原植入致敏正常小鼠和CD100缺陷（CD100(-/-)）小鼠的肾小球中，诱导实验性新月体性肾小球肾炎。CD100(-/-)小鼠的肾小球出现新月体形成或严重组织学改变的较少。CD100(-/-)小鼠的抗原特异性免疫反应降低。脾细胞产生的干扰素（IFN）-γ和白细胞介素（IL）-4减少，免疫的CD100(-/-)小鼠淋巴结中活化的T细胞和B细胞较少。血清抗原特异性免疫球蛋白（IgG）水平也降低。肾小球巨噬细胞和CD4(+)细胞浸润以及IgG和C3沉积减弱。正常肾脏表达CD100和丛状蛋白-B1（CD100的组织受体）的mRNA。直接免疫荧光显示，肾脏中的CD100蛋白主要存在于肾小管中，而丛状蛋白-B1同时存在于肾小球和肾小管中。为了确定肾小球丛状蛋白-B1是否通过白细胞CD100介导白细胞募集，在被动转移异源抗体（吸引中性粒细胞）或同源抗体（吸引巨噬细胞）后研究了募集情况。CD100(-/-)小鼠的肾小球巨噬细胞减少，但中性粒细胞募集相当，这与巨噬细胞而非中性粒细胞上的CD100表达一致。CD100促进严重的致肾炎性免疫反应，白细胞CD100-肾小球丛状蛋白-B1相互作用增强巨噬细胞向肾小球的募集。
