Brown Kevin N, Trichel Anita, Barratt-Boyes Simon M
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
J Immunol. 2007 Jun 1;178(11):6958-67. doi: 10.4049/jimmunol.178.11.6958.
The loss of myeloid (mDC) and plasmacytoid dendritic cells (pDC) from the blood of HIV-infected individuals is associated with progressive disease. It has been proposed that DC loss is due to increased recruitment to lymph nodes, although this has not been directly tested. Similarly as in HIV-infected humans, we found that lineage-negative (Lin(-)) HLA-DR(+)CD11c(+)CD123(-) mDC and Lin(-)HLA-DR(+)CD11c(-)CD123(+) pDC were lost from the blood of SIV-infected rhesus macaques with AIDS. In the peripheral lymph nodes of SIV-naive monkeys the majority of mDC were mature cells derived from skin that expressed high levels of HLA-DR, CD83, costimulatory molecules, and the Langerhans cell marker CD1a, whereas pDC expressed low levels of HLA-DR and CD40 and lacked costimulatory molecules, similar to pDC in blood. Surprisingly, both DC subsets were depleted from peripheral and mesenteric lymph nodes and spleens in monkeys with AIDS, although the activation status of the remaining DC subsets was similar to that of DC in health. In peripheral and mesenteric lymph nodes from animals with AIDS there was an accumulation of Lin(-)HLA-DR(moderate)CD11c(-)CD123(-) cells that resembled monocytoid cells but failed to acquire a DC phenotype upon culture, suggesting they were not DC precursors. mDC and pDC from the lymphoid tissues of monkeys with AIDS were prone to spontaneous death in culture, indicating that apoptosis may be a mechanism for their loss in disease. These findings demonstrate that DC are lost from rather than recruited to lymphoid tissue in advanced SIV infection, suggesting that systemic DC depletion plays a direct role in the pathophysiology of AIDS.
HIV感染个体血液中髓样树突状细胞（mDC）和浆细胞样树突状细胞（pDC）的缺失与疾病进展相关。有人提出树突状细胞的缺失是由于向淋巴结的募集增加，尽管这尚未得到直接验证。与HIV感染的人类情况类似，我们发现，在患有艾滋病的感染猴免疫缺陷病毒（SIV）的恒河猴血液中，谱系阴性（Lin(-)）HLA-DR(+)CD11c(+)CD123(-) mDC和Lin(-)HLA-DR(+)CD11c(-)CD123(+) pDC缺失。在未感染SIV的猴子外周淋巴结中，大多数mDC是源自皮肤的成熟细胞，表达高水平的HLA-DR、CD83、共刺激分子以及朗格汉斯细胞标志物CD1a，而pDC表达低水平的HLA-DR和CD40且缺乏共刺激分子，这与血液中的pDC相似。令人惊讶的是，在患有艾滋病的猴子中，外周和肠系膜淋巴结以及脾脏中的这两种树突状细胞亚群均被耗尽，尽管剩余树突状细胞亚群的激活状态与健康状态下的树突状细胞相似。在患有艾滋病动物的外周和肠系膜淋巴结中，出现了Lin(-)HLA-DR（中等）CD11c(-)CD123(-)细胞的积聚，这些细胞类似单核细胞样细胞，但在培养时未能获得树突状细胞表型，表明它们不是树突状细胞前体。患有艾滋病的猴子淋巴组织中的mDC和pDC在培养中易于自发死亡，这表明细胞凋亡可能是它们在疾病中缺失的一种机制。这些发现表明，在晚期SIV感染中，树突状细胞是从淋巴组织中丢失而非被募集到淋巴组织中，这表明全身性树突状细胞耗竭在艾滋病的病理生理学中起直接作用。
