De Wit D, Van Mechelen M, Zanin C, Doutrelepont J M, Velu T, Gérard C, Abramowicz D, Scheerlinck J P, De Baetselier P, Urbain J
Département de Biologie Moléculaire, Université Libre de Bruxelles, Belgium.
J Immunol. 1993 Jan 15;150(2):361-6.
The injection of DBA/2 parental lymphocytes into adult, immunologically intact (C57BL/6 x DBA/2) F1 hybrid mice results in a chronic graft-vs-host reaction (GVHR) characterized by a deficiency in CD4+ T cell functions and a B cell activation leading to autoantibody production. The discovery that distinct subpopulations of Th cells may regulate the effector immune functions led us to investigate whether the chronic GVHR differentially affects Th subsets. Data are presented indicating that mice undergoing a GVHR spontaneously produced lymphokines of Th2 origin. IL-4 and IL-10 mRNA were detected in the spleens of GVH mice, and IL-4 was shown to be responsible for the increased expression of class II Ag on B cells. Moreover, upon polyclonal activation in vitro, GVH T cells exhibited defective IL-2 and IFN-gamma production but elevated IL-4 production. We conclude that the chronic GVHR is characterized by a selective deficiency in cells secreting IL-2 and IFN-gamma and a hyperactivation of Th2 cells. The simultaneous production of IL-4 and IL-10 might explain the association between B cell hyperactivity and impairment of Th1-like activities in various models that associate autoimmunity and immunosuppression, such as GVHR and HIV infection.
将DBA/2亲代淋巴细胞注射到成年、免疫功能完整的（C57BL/6×DBA/2）F1杂交小鼠中会引发慢性移植物抗宿主反应（GVHR），其特征为CD4+T细胞功能缺陷以及B细胞活化并导致自身抗体产生。不同亚群的Th细胞可能调节效应免疫功能这一发现促使我们研究慢性GVHR是否对Th亚群产生不同影响。所呈现的数据表明，经历GVHR的小鼠会自发产生Th2来源的淋巴因子。在GVH小鼠的脾脏中检测到IL-4和IL-10 mRNA，并且IL-4被证明是导致B细胞上II类抗原表达增加的原因。此外，在体外多克隆激活后，GVH T细胞表现出IL-2和IFN-γ产生缺陷，但IL-4产生增加。我们得出结论，慢性GVHR的特征是分泌IL-2和IFN-γ的细胞选择性缺陷以及Th2细胞的过度活化。IL-4和IL-10的同时产生可能解释了在各种将自身免疫和免疫抑制相关联的模型中，如GVHR和HIV感染，B细胞过度活跃与Th1样活性受损之间的关联。
