Daniel V, Süsal C, Weimer R, Zimmermann R, Huth-Kühne A, Opelz G
Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Germany.
AIDS Res Hum Retroviruses. 2001 Mar 1;17(4):329-35. doi: 10.1089/08892220150503690.
Previous studies interpreted increases of soluble Fas (sFas) in the plasma during disease progression in HIV-infected patients as evidence of increased apoptosis of CD4(+) lymphocytes. We studied whether sFas and sFas ligand (sFasL) plasma levels are associated with CD4(+) and CD8(+) lymphocyte counts, plasma viral load, and IgM, IgG, C3d, and gp120 complexes on circulating CD4(+) blood lymphocytes in long-term surviving HIV-infected hemophilia patients, most of whom were receiving HAART. Twenty-six hemophilia patients who were infected with HIV in the early 1980s were investigated in 1997, 1998, and 1999. HAART was initiated in 1996 and 1997 in most patients. Lymphocyte subpopulations and immune complex-coated CD4(+) lymphocytes in the blood were investigated by flow cytometry, plasma viral load (HIV-1 mRNA copies/ml plasma) was tested with HIV-1 QT Nuclisens kits, sFas (ng/ml) and sFasL (ng/ml) plasma levels were measured with MBL ELISA kits, and the in vitro response of patient lymphocytes was tested in cell cultures. During the period from 1997 to 1999 we observed an increase in sFas plasma levels (p = 0.003) as well as in CD4(+) (p = 0.004) and CD8(+) (p = 0.023) cell counts; a decrease in IgG (p = 0.047), C3d (p = 0.024), and gp120 (p = 0.001)-coated CD4(+) lymphocytes in the blood; and a decrease in the number of impaired mitogen stimulation assays (p = 0.013). sFas was negatively associated with viral burden (r = -0.662, p = 0.0002) as well as with CD4(+)IgM(+) (r = -0.554, p = 0.004), CD4(+)IgG(+) (r = -0.431, p = 0.031), CD4(+)C3d(+) (r = -0.551, p = 0.041), and CD4(+)gp120(+) (r = -0.430, p = 0.041) blood lymphocytes, CD8(+)DR(+) cell counts (r = -0.700, p = 0.016), and impaired in vitro responses of patient lymphocytes to PHA (r = -0.475, p = 0.016). sFasL was negatively associated with total lymphocyte counts (r = -0.433, p = 0.027), as well as with absolute numbers of CD3(+) (r = -0.492, p = 0.011) and CD8(+) (r = -0.432, p = 0.027) cells. We conclude that, contrary to expectations, sFas plasma levels increased in long-term surviving HIV-infected hemophilia patients receiving HAART, concomitant with increases in CD4(+) and CD8(+) cell counts. Increased sFas may reflect the growing pool of T lymphocytes that recovers because of a decreasing viral burden and a decreasing immune complex load of CD4(+) lymphocytes.
先前的研究将HIV感染患者疾病进展过程中血浆中可溶性Fas（sFas）的增加解释为CD4(+)淋巴细胞凋亡增加的证据。我们研究了长期存活的HIV感染血友病患者（其中大多数正在接受高效抗逆转录病毒治疗[HAART]）的血浆sFas和sFas配体（sFasL）水平是否与CD4(+)和CD8(+)淋巴细胞计数、血浆病毒载量以及循环CD4(+)血液淋巴细胞上的IgM、IgG、C3d和gp120复合物相关。1997年、1998年和1999年对26名在20世纪80年代初感染HIV的血友病患者进行了调查。大多数患者于1996年和1997年开始接受HAART。通过流式细胞术研究血液中的淋巴细胞亚群和免疫复合物包被的CD4(+)淋巴细胞，使用HIV-1 QT Nuclisens试剂盒检测血浆病毒载量（每毫升血浆中HIV-1 mRNA拷贝数），使用MBL ELISA试剂盒测量血浆sFas（纳克/毫升）和sFasL（纳克/毫升）水平，并在细胞培养中检测患者淋巴细胞的体外反应。在1997年至1999年期间，我们观察到血浆sFas水平升高（p = 0.003）以及CD4(+)（p = 0.004）和CD8(+)（p = 0.023）细胞计数增加；血液中IgG（p = 0.047）、C3d（p = 0.024）和gp120（p = 0.001）包被的CD4(+)淋巴细胞减少；有丝分裂原刺激试验受损的数量减少（p = 0.013）。sFas与病毒载量呈负相关（r = -0.662，p = 0.0002），也与CD4(+)IgM(+)（r = -0.554，p = 0.004）、CD4(+)IgG(+)（r = -0.431，p = 0.031）、CD4(+)C3d(+)（r = -0.551，p = 0.041）和CD4(+)gp120(+)（r = -0.430，p = 0.041）血液淋巴细胞、CD8(+)DR(+)细胞计数（r = -0.700，p = 0.016）以及患者淋巴细胞对PHA的体外反应受损（r = -0.475，p = 0.016）呈负相关。sFasL与总淋巴细胞计数呈负相关（r = -0.433，p = 0.027），也与CD3(+)（r = -0.492，p = 0.011）和CD8(+)（r = -0.432，p = 0.027）细胞的绝对数量呈负相关。我们得出结论，与预期相反，接受HAART的长期存活HIV感染血友病患者血浆sFas水平升高，同时CD4(+)和CD8(+)细胞计数增加。sFas升高可能反映了由于病毒载量降低和CD4(+)淋巴细胞免疫复合物负荷减少而恢复的T淋巴细胞池不断扩大。
