Lenkei R, Bratt G, Holmberg V, Muirhead K, Sandström E
CALAB Research, S:t. Görans Hospital, Stockholm, Sweden.
Cytometry. 1998 Oct 1;33(2):115-22. doi: 10.1002/(sici)1097-0320(19981001)33:2<115::aid-cyto5>3.0.co;2-i.
Increased activation of CD8+ T cells, particularly increased expression of CD38 antigen, has been shown to strongly correlate with progression of human immunodeficiency virus-positive (HIV+) individuals to acquired immunodeficiency syndrome (AIDS) and death. As part of a study evaluating responses to a recombinant gp160 vaccine, we have used quantitative three-color flow cytometry (QFCM) to further investigate the relationships among several measures of lymphocyte activation/immunological status. Parameters evaluated included 1) absolute circulating counts for the major lymphocyte phenotypes (T, B, NK) and selected activated/regulatory subsets believed to have clinical value in the monitoring of patients with HIV infection; 2) level of CD38 expression (antibody-binding capacity [ABC]) on the lymphocyte subsets defined by CD8, CD38, and HLA-DR; and 3) serum levels of soluble CD8. CD8+DR+CD38+ counts were found to be markedly increased (approximately 10-fold) in HIV+ individuals, whereas CD4+CD45RA+ counts were markedly decreased (approximately 5-fold). We confirmed previous reports that CD38 expression on CD8 T cells (here reported as CD38 ABC) are increased in asymptomatic HIV+ individuals as compared with healthy controls, and further found that CD38 ABC was elevated approximately 2-fold on CD8+DR+ cells as compared with CD8+DR- cells in healthy controls, and almost 2-fold further elevated on CD8+DR+ cells in HIV+ individuals compared with CD8+DR+ cells in healthy controls. In agreement with previous studies, we found increased serum CD8 levels (sCD8) and increased CD8+DR+ counts in asymptomatic HIV+ individuals. However, when sCD8 was expressed relative to CD8+DR+ cell counts (RsCD8), this index was found to be significantly decreased in HIV+ individuals. Although CD38 ABC on CD8+DR+ cells showed no correlation with sCD8, it was significantly correlated with RsCD8 in both HIV+ and HIV- individuals. Absolute lymphocyte counts were strongly correlated with both CD38 ABC and RsCD8 in HIV+ individuals. However, CD4 counts were correlated with CD38 ABC (but not RsCD8) in HIV+ patients and with RsCD8 (but not CD38 ABC) in HIV-controls. Our results suggest that QFCM is significant in understanding the role of CD8+DR+CD38+ cells in processes such as lymphocyte homeostasis and HIV-induced CD4-cell depletion.
已表明，CD8 + T细胞的激活增加，尤其是CD38抗原表达的增加，与人类免疫缺陷病毒阳性（HIV +）个体发展为获得性免疫缺陷综合征（AIDS）及死亡密切相关。作为评估对重组gp160疫苗反应的一项研究的一部分，我们使用定量三色流式细胞术（QFCM）进一步研究了淋巴细胞激活/免疫状态的几种测量指标之间的关系。评估的参数包括：1）主要淋巴细胞表型（T、B、NK）以及选定的激活/调节亚群的绝对循环计数，这些亚群被认为在监测HIV感染患者中具有临床价值；2）由CD8、CD38和HLA - DR定义的淋巴细胞亚群上的CD38表达水平（抗体结合能力[ABC]）；3）可溶性CD8的血清水平。发现HIV +个体中CD8 + DR + CD38 +计数显著增加（约10倍），而CD4 + CD45RA +计数显著减少（约5倍）。我们证实了先前的报道，即与健康对照相比，无症状HIV +个体中CD8 T细胞上的CD38表达（此处报告为CD38 ABC）增加，并且进一步发现，与健康对照中的CD8 + DR -细胞相比，健康对照中CD8 + DR +细胞上的CD38 ABC升高约2倍，而与健康对照中的CD8 + DR +细胞相比，HIV +个体中CD8 + DR +细胞上的CD38 ABC又几乎升高2倍。与先前的研究一致，我们发现无症状HIV +个体中血清CD8水平（sCD8）升高且CD8 + DR +计数增加。然而，当sCD8相对于CD8 + DR +细胞计数（RsCD8）表达时，发现该指标在HIV +个体中显著降低。尽管CD8 + DR +细胞上的CD38 ABC与sCD8无相关性，但在HIV +和HIV -个体中均与RsCD8显著相关。在HIV +个体中，绝对淋巴细胞计数与CD38 ABC和RsCD8均密切相关。然而，在HIV +患者中，CD4计数与CD38 ABC相关（但与RsCD8无关），而在HIV对照中与RsCD8相关（但与CD38 ABC无关）。我们的结果表明，QFCM对于理解CD8 + DR + CD38 +细胞在淋巴细胞稳态和HIV诱导的CD4细胞耗竭等过程中的作用具有重要意义。
