Howard Kristina E, Burkhard Mary Jo
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA.
AIDS Res Hum Retroviruses. 2007 May;23(5):720-8. doi: 10.1089/aid.2006.0025.
Studies of human immunodeficiency virus-1 (HIV-1)-infected patients and simian immunodeficiency virus (SIV)-infected macaques have identified profound depletion of CD4(+) T cells and expansion of CD8(+) T cells in the gastrointestinal lamina propria. Less attention has been given to CD8(+) intraepithelial lymphocytes (IEL), and no studies have concurrently examined inductive sites such as draining lymph nodes. Our preliminary data in the feline immunodeficiency virus (FIV) animal model suggested additional changes in IEL, and marked differences in the responses of lymph nodes draining different mucosal sites. To address this, we quantified the absolute leukocyte yield and examined the phenotype of cells from small intestinal IEL, mesenteric lymph node (MLN), and medial iliac lymph node (ILN) from chronically FIV-infected cats. The cellularity of the ILN was increased 530% in FIV-infected animals with an expansion of CD62L(+) cells, suggesting an increased population of naive T cells. The number of CD4(+), as well as CD8(+), T cells was increased in the ILN, resulting in a CD4:CD8 ratio greater than 1:1. In contrast, reduced cellularity, specific loss of CD4(+) T cells, and inversion of the CD4:CD8 ratio was observed in the MLN, which drains the intestine. In IEL, loss of CD8alpha, CD8beta, and CD4-expressing T cells was found in FIV-infected cats. Furthermore, expression intensity of CD8alpha and CD5, markers known to be important in T cell function, was markedly decreased on IEL. These findings expand the array of immune alterations induced by lentiviral infection and indicate that characterization of multiple mucosal sites will be necessary to fully understand the pathogenesis of HIV-1 infection.
对人类免疫缺陷病毒1型（HIV-1）感染患者和猿猴免疫缺陷病毒（SIV）感染猕猴的研究发现，胃肠道固有层中CD4(+) T细胞严重耗竭，CD8(+) T细胞扩增。人们对CD8(+) 上皮内淋巴细胞（IEL）的关注较少，且尚无研究同时检测引流淋巴结等诱导部位。我们在猫免疫缺陷病毒（FIV）动物模型中的初步数据表明，IEL存在其他变化，且引流不同黏膜部位的淋巴结反应存在显著差异。为解决这一问题，我们对慢性FIV感染猫的小肠IEL、肠系膜淋巴结（MLN）和髂内侧淋巴结（ILN）中的白细胞绝对产量进行了量化，并检测了细胞表型。FIV感染动物的ILN细胞数量增加了530%，CD62L(+) 细胞扩增，提示幼稚T细胞群体增加。ILN中CD4(+) 和CD8(+) T细胞数量均增加，导致CD4:CD8比值大于1:1。相比之下，引流肠道的MLN细胞数量减少，CD4(+) T细胞特异性丢失，CD4:CD8比值倒置。在IEL中，FIV感染猫出现CD8α、CD8β和表达CD4的T细胞丢失。此外，IEL上已知在T细胞功能中起重要作用的标志物CD8α和CD5的表达强度显著降低。这些发现扩展了慢病毒感染诱导的免疫改变范围，并表明要全面了解HIV-1感染的发病机制，有必要对多个黏膜部位进行表征。
