Yu P, Morawetz R A, Chattopadhyay S, Makino M, Kishimoto T, Kikutani H
Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
Eur J Immunol. 1999 Feb;29(2):615-25. doi: 10.1002/(SICI)1521-4141(199902)29:02<615::AID-IMMU615>3.0.CO;2-I.
CD40-deficient mice, when inoculated with the LP-BM5def murine retorvirus, become infected and show virus expression similar to wild-type mice. However, unlike the wild-type mice, CD40-deficient mice do not develop symptoms of immunodeficiency, lymphoproliferative disease and the typical histological changes in the lymphoid tissue. These results show that the CD40-CD40 ligand (CD40L) interaction in vivo is essential for anergy induction and the subsequent development of immunodeficiency and pathologic expansion of lymphocytes. Infected CD40-deficient mice and their littermates express a similar pattern of cytokine mRNA, which is not biased towards a Th2 phenotype. Nevertheless, hypergammaglobulinemia is induced in infected wild-type and CD40-deficient mice. Surprisingly, murine AIDS infection even induces IgE production in CD40-deficient mice in vivo. Our data demonstrate that antibody class switch to IgE and IgG1 can be induced by a retroviral infection in vivo even in the absence of CD40-CD40L interaction and an apparent switch to a Th2 cytokine production.
用LP - BM5def鼠逆转录病毒接种CD40缺陷小鼠后,它们会被感染并表现出与野生型小鼠相似的病毒表达。然而,与野生型小鼠不同的是,CD40缺陷小鼠不会出现免疫缺陷症状、淋巴增殖性疾病以及淋巴组织典型的组织学变化。这些结果表明,体内CD40 - CD40配体(CD40L)相互作用对于无反应性诱导以及随后免疫缺陷的发展和淋巴细胞的病理性扩增至关重要。感染的CD40缺陷小鼠及其同窝小鼠表达相似模式的细胞因子mRNA,且不偏向于Th2表型。尽管如此,感染的野生型和CD40缺陷小鼠均会诱导产生高球蛋白血症。令人惊讶的是,鼠类艾滋病感染甚至能在体内诱导CD40缺陷小鼠产生IgE。我们的数据表明,即使在没有CD40 - CD40L相互作用以及明显向Th2细胞因子产生转变的情况下,体内逆转录病毒感染也能诱导抗体类别转换为IgE和IgG1。