Itescu S, Dalton J, Zhang H Z, Winchester R
Department of Pediatrics, Columbia University, College of Physicians and Surgeons, New York 10032.
J Clin Invest. 1993 May;91(5):2216-25. doi: 10.1172/JCI116448.
HIV-1 infection may initiate to an HLA-associated response designated diffuse infiltrative lymphocytosis syndrome, characterized by increased numbers of circulating CD8 T cells that infiltrate salivary glands, lungs, gastrointestinal tract, and kidneys. Since this response could either be an antigenically driven process induced by HIV-1 or a lymphoproliferation of cells with neoplastic or unusual features, we sought to define the phenotype of the cellular populations, the nature of tissue derangement, and the tissue localization of virus in diffuse infiltrative lymphocytosis syndrome. Circulating CD8 T cells were greatly increased while CD4 T cell numbers remained in the range found in asymptomatic seropositive persons. The majority of CD8 and CD4 T cells in both blood and tissues had the memory phenotype of CD29+ (beta 1 integrin) and CD11a+/CD18 (beta 2 integrin) expression, but lacked markers of recent activation. A proportion of the circulating CD8 T cells also expressed CD57 (Leu 7) but not other markers of natural killer cells. HIV-encoded proteins were identified in tissue macrophages located in periacinar areas of the salivary glands. CD54 (intercellular adhesion molecule-1), a ligand for the CD11a integrin, was strongly expressed on postcapillary venule endothelium within lymphoid foci, and HLA-DR molecules were found on limited regions of ductular epithelium adjacent to lymphoid aggregates. These findings suggest that (a) the visceral lymphocytic infiltration in diffuse infiltrative lymphocytosis syndrome is an antigen-driven, and MHC-determined, host immune response to an element associated with HIV-1 infection, and (b) that the specific adhesive molecule interactions mediating the cellular influx, as well as the subsequent tissue damage, reflect altered patterns of gene expression in tissues undergoing an immune response.
HIV-1感染可能引发一种与HLA相关的反应，即弥漫性浸润性淋巴细胞增多综合征，其特征是循环CD8 T细胞数量增加，这些细胞浸润唾液腺、肺、胃肠道和肾脏。由于这种反应可能是由HIV-1诱导的抗原驱动过程，也可能是具有肿瘤或异常特征的细胞的淋巴细胞增殖，我们试图确定弥漫性浸润性淋巴细胞增多综合征中细胞群体的表型、组织紊乱的性质以及病毒在组织中的定位。循环CD8 T细胞大幅增加，而CD4 T细胞数量仍处于无症状血清阳性者的范围内。血液和组织中的大多数CD8和CD4 T细胞具有CD29+（β1整合素）和CD11a+/CD18（β2整合素）表达的记忆表型，但缺乏近期激活的标志物。一部分循环CD8 T细胞也表达CD57（Leu 7），但不表达其他自然杀伤细胞标志物。在位于唾液腺腺泡周围区域的组织巨噬细胞中鉴定出了HIV编码的蛋白。CD54（细胞间粘附分子-1）是CD11a整合素的配体，在淋巴滤泡内的毛细血管后微静脉内皮上强烈表达，并且在与淋巴聚集物相邻的导管上皮的有限区域发现了HLA-DR分子。这些发现表明：（a）弥漫性浸润性淋巴细胞增多综合征中的内脏淋巴细胞浸润是一种抗原驱动的、由MHC决定的宿主对与HIV-1感染相关元素的免疫反应；（b）介导细胞流入以及随后组织损伤的特定粘附分子相互作用反映了正在经历免疫反应的组织中基因表达模式的改变。
