Hu J, Pope M, Brown C, O'Doherty U, Miller C J
California Regional Primate Research Center, School of Veterinary Medicine, University of California, Davis 95616, USA.
Lab Invest. 1998 Apr;78(4):435-51.
Significant progress has been made in understanding the biology of heterosexual transmission of HIV by utilizing the simian immunodeficiency virus (SIV)/rhesus monkey animal model. Our previous studies have shown that SIV-infected cells within the stratified squamous epithelium of the vagina have a dendritic morphology. However, the type of cell infected was not conclusively determined. The purpose of the present study was to immunophenotype the SIV-infected cells in the lower reproductive tract and genital lymph nodes of the female rhesus monkey. Vagina, cervix, and iliac lymph node from eight chronically SIV-infected adult female monkeys were examined for this study. None of the animals had histologic evidence of opportunistic infections or genital tract pathogens other than SIV. Combined in situ hybridization and immunohistochemistry were used to detect SIV RNA and to determine the immunophenotype of SIV-infected cells in tissue sections and cytospin preparations of cells from the tissues. We now show that SIV-infected cells were most common in iliac lymph node and that the majority of infected cells in the lymph node were T lymphocytes. SIV-infected macrophages, Langerhans' cells, and dendritic cells were also found in the lymph node. SIV-infected cells were found within the epithelium and lamina propria of the vagina. Although most of the infected cells were T cells, a significant proportion (approximately 40%) of the SIV-infected cells in cytospin preparations from explant cultures of vagina and cervix were Langerhans' cells. SIV-infected T cells in the lower genital tract were commonly associated with focal mononuclear cell infiltrates. SIV-infected macrophages were rarely found in the genital tract. The present study provides the first direct demonstration that Langerhans' cells and dendritic cells in the genital tract and lymph nodes are infected with SIV in vivo. Thus, dendritic cells, in general, and Langerhans' cells, in particular, are important reservoirs for HIV/SIV replication in vivo.
通过利用猿猴免疫缺陷病毒(SIV)/恒河猴动物模型,在了解HIV异性传播生物学方面取得了重大进展。我们之前的研究表明,阴道复层鳞状上皮内感染SIV的细胞具有树突状形态。然而,被感染细胞的类型尚未最终确定。本研究的目的是对雌性恒河猴下生殖道和生殖器官淋巴结中感染SIV的细胞进行免疫表型分析。本研究检查了8只慢性感染SIV的成年雌性恒河猴的阴道、子宫颈和髂淋巴结。除了SIV外,没有一只动物有机会性感染或生殖道病原体的组织学证据。联合原位杂交和免疫组织化学用于检测SIV RNA,并确定组织切片和来自这些组织的细胞的细胞涂片制备物中感染SIV的细胞的免疫表型。我们现在表明,SIV感染的细胞在髂淋巴结中最常见,并且淋巴结中大多数被感染的细胞是T淋巴细胞。在淋巴结中也发现了感染SIV的巨噬细胞、朗格汉斯细胞和树突状细胞。在阴道的上皮和固有层中发现了感染SIV的细胞。虽然大多数被感染的细胞是T细胞,但在阴道和子宫颈外植体培养物的细胞涂片制备物中,相当比例(约40%)的感染SIV的细胞是朗格汉斯细胞。下生殖道中感染SIV的T细胞通常与局灶性单核细胞浸润有关。在生殖道中很少发现感染SIV的巨噬细胞。本研究首次直接证明,生殖道和淋巴结中的朗格汉斯细胞和树突状细胞在体内被SIV感染。因此,一般来说,树突状细胞,特别是朗格汉斯细胞,是体内HIV/SIV复制的重要储存库。