Rahmouni Souad, Aandahl Einar Martin, Nayjib Btissam, Zeddou Mustapha, Giannini Sandra, Verlaet Myriam, Greimers Roland, Boniver Jaques, Tasken Kjetil, Moutschen Michel
Department of Pathology, University of Liège, B-4000 Liège, Belgium.
Biochem J. 2004 Dec 15;384(Pt 3):469-76. doi: 10.1042/BJ20031859.
MAIDS (murine AIDS) is caused by infection with the murine leukaemia retrovirus RadLV-Rs and is characterized by a severe immunodeficiency and T-cell anergy combined with a lymphoproliferative disease affecting both B- and T-cells. Hyperactivation of the cAMP-protein kinase A pathway is involved in the T-cell dysfunction of MAIDS and HIV by inhibiting T-cell activation through the T-cell receptor. In the present study, we show that MAIDS involves a strong and selective up-regulation of cyclo-oxygenase type 2 in the CD11b+ subpopulation of T- and B-cells of the lymph nodes, leading to increased levels of PGE2 (prostaglandin E2). PGE2 activates the cAMP pathway through G-protein-coupled receptors. Treatment with cyclo-oxygenase type 2 inhibitors reduces the level of PGE2 and thereby reverses the T-cell anergy, restores the T-cell immune function and ameliorates the lymphoproliferative disease.
小鼠获得性免疫缺陷综合征（MAIDS）由感染鼠白血病逆转录病毒RadLV-Rs引起，其特征为严重免疫缺陷、T细胞无反应性，并伴有影响B细胞和T细胞的淋巴细胞增生性疾病。环磷酸腺苷-蛋白激酶A途径的过度激活通过抑制T细胞受体介导的T细胞活化，参与了MAIDS和HIV的T细胞功能障碍。在本研究中，我们发现MAIDS涉及淋巴结中T细胞和B细胞的CD11b+亚群中环氧合酶-2的强烈且选择性上调，导致前列腺素E2（PGE2）水平升高。PGE2通过G蛋白偶联受体激活环磷酸腺苷途径。用环氧合酶-2抑制剂治疗可降低PGE2水平，从而逆转T细胞无反应性，恢复T细胞免疫功能，并改善淋巴细胞增生性疾病。
