Establishment of Acquired Immune Deficiency Mouse Model, and Its Mycobacterium intracellulare Infection.

近年来，许多获得性免疫缺陷综合征(AIDS)患者被报道有频繁的细胞内分支杆菌感染。但他们两人的治疗都相当不满意。我们建立了小鼠细胞内分枝杆菌感染模型，并利用该模型进一步探讨了其感染的治疗方法。为建立小鼠免疫缺陷模型，用抗小鼠Thy1.2单抗免疫细胞内分枝杆菌感染模型小鼠。但是，不满意的免疫抑制是值得争取的。因此，我们决定首先研究分枝杆菌感染的炎症细胞动力学。通过全肺灌洗(TPL)回收炎性细胞，并用抗Thy1.2、Lyt-2(CD8)、L3T4(CD4)和Ia的单抗进行染色。用流式细胞仪检测细胞表面抗原表达。在感染过程中行TPLs手术。Thy1.2阳性和Lyt-2阳性淋巴细胞在感染后即刻增加，而L3T4阳性淋巴细胞和Ia阳性巨噬细胞在感染后3周逐渐增加。Thy1.2阳性淋巴细胞和Ia阳性巨噬细胞在感染后6周达到平台期。反之，Lyt-2阳性和L3T4阳性淋巴细胞随着其表面抗原表达比率的上升和下降，并有一个反向旋转的过程，好像它们是相互反馈控制的。在下一步，研究了生物反应调节剂(BRM)的效果。用重组白介素2(rIL-2)、Muramyl二肽衍生物、DJ-7041和环孢菌素A(CyA)治疗小鼠细胞内支原体感染。观察rIL-2处理的小鼠感染早期Ia阳性巨噬细胞和DJ-7041处理的小鼠感染晚期Ia阳性巨噬细胞的增加情况。利用这一模型，我们将建立类似于艾滋病合并细胞内支原体感染的免疫缺陷小鼠模型。

Recently many patients with acquired immune deficiency syndrome (AIDS) were reported to have frequent Mycobacterium intracellulare infection. But the treatment of both of them were quite unsatisfactory. We have established the M.intracellulare infection mouse model, and by using it, have investigated about the treatment of its infection further. For the purpose of establish the immune deficiency model, nomoclonal anti-mouse Thy1.2 antibody was administered to the M.intracellulare infection model mice. but unsatisfied immune depression was earned. So we decided to investigate the inflammatory cell dynamics for the mycobacterial infection at first. Inflammatory cells were recovered by total pulmonary lavage (TPL) and stained with monoclonal anti-Thy1.2, Lyt-2(CD8), L3T4(CD4), and Ia. The cell surface antigen expression were measured by flow cytometrical cell analizer. Tpls were performed during the course of infection. Thy1.2 positive and Lyt-2 positive lymphocytes were increased soon after the infection, but the L3T4 positive lymphocytes and Ia positive macrophages were gradually increased three weeks after infection. Thy1.2 positive lymphocytes and Ia positive macrophages reached the plateau six weeks after infection. On the contraty, Lyt-2 positive and L3T4 positive lymphocytes were up and down with their surface antigen expression ratio and have a contra-rotation course as if they were feed back controlled each other. For the next step, the effects of biological response modifiers (BRMs) were investigated. Recombinant interleukin-2 (rIL-2), Muramyl dipeptide derivative; DJ-7041 and cyclosporin A (CyA) were administered to the M.intracellulare infection mice. The increase of Ia positive macrophages at the early stage after infection by rIL-2 treated mice and at the late stage by DJ-7041 treated mice were observed. By using this model we are going to establish the immune deficiency mouse model akin to the AIDS with M.intracellulare infection.