Killian M Scott, Fujimura Sue H, Hecht Frederick M, Levy Jay A
Department of Medicine, University of California-San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
AIDS. 2006 Jun 12;20(9):1247-52. doi: 10.1097/01.aids.0000232231.34253.bd.
Reduced dendritic cell (DC) frequencies and functions in individuals with longstanding HIV-1 infection are predictive of opportunistic infections and AIDS. To investigate possible early alterations in DC levels after HIV infection, we prospectively examined plasmacytoid dendritic cell (pDC) and myeloid dendritic cell (mDC) frequencies and plasma IFN-alpha levels in patients undergoing primary HIV-1 infection (PHI).
Peripheral blood DC frequencies and absolute counts were determined by flow cytometry. Plasma IFN-alpha levels were measured by enzyme-linked immunosorbent assay (ELISA).
In comparison to uninfected subjects, pDC, but not mDC, levels were reduced (P < 0.001) in subjects with PHI, especially in those with high viral loads or low CD4 T-cell counts. During 24-48 weeks of observation, untreated subjects experienced slight declines in pDC and CD4 T-cell levels. In contrast, subjects initiating early antiretroviral therapy (ART) exhibited increases (P < 0.001) in pDC and CD4 T-cell counts. No effect of treatment on mDC counts was observed. Circulating plasma IFN-alpha was undetectable by ELISA regardless of the duration of HIV-1 infection.
PHI is characterized by a reduction in pDC and CD4 T-cell counts that correlates with the magnitude of virus replication and is not evidenced by the mDC count or plasma IFN-alpha level. Early ART appears to have similar restorative effects on pDC and CD4 T-cell counts.
在长期感染HIV-1的个体中,树突状细胞(DC)频率和功能降低可预测机会性感染和艾滋病。为了研究HIV感染后DC水平可能出现的早期变化,我们前瞻性地检测了原发性HIV-1感染(PHI)患者的浆细胞样树突状细胞(pDC)和髓样树突状细胞(mDC)频率以及血浆IFN-α水平。
通过流式细胞术测定外周血DC频率和绝对计数。采用酶联免疫吸附测定(ELISA)法检测血浆IFN-α水平。
与未感染的受试者相比,PHI患者的pDC水平降低(P < 0.001),而mDC水平未降低,尤其是在病毒载量高或CD4 T细胞计数低的患者中。在观察的24至48周期间,未接受治疗的受试者的pDC和CD4 T细胞水平略有下降。相比之下,开始早期抗逆转录病毒治疗(ART)的受试者的pDC和CD4 T细胞计数增加(P < 0.001)。未观察到治疗对mDC计数有影响。无论HIV-1感染持续时间如何,ELISA均未检测到循环血浆IFN-α。
PHI的特征是pDC和CD4 T细胞计数减少,这与病毒复制程度相关,而mDC计数或血浆IFN-α水平未显示出这种变化。早期ART似乎对pDC和CD4 T细胞计数具有相似的恢复作用。