Kurane I, Innis B L, Nimmannitya S, Nisalak A, Meager A, Janus J, Ennis F A
Department of Medicine, University of Massachusetts Medical Center, Worcester 01655.
J Clin Invest. 1991 Nov;88(5):1473-80. doi: 10.1172/JCI115457.
It has been reported that the severe complication of dengue virus infection, dengue hemorrhagic fever (DHF) is much more commonly observed during secondary dengue virus infections than primary infections. In order to elucidate the role of T lymphocytes in the pathogenesis of DHF, we attempted to determine whether T lymphocytes are activated in vivo during dengue virus infections, by examining the levels of soluble IL-2 receptor (sIL-2R), soluble CD4 (sCD4), soluble CD8 (sCD8), interleukin-2 (IL-2) and interferon-gamma (IFN gamma) in the sera of 59 patients with DHF and 41 patients with dengue fever (DF). The levels of sIL-2R, sCD4, sCD8, IL-2, and IFN gamma were significantly higher in the acute sera of patients with DHF than in the sera of healthy children (P less than 0.001 for all markers). The acute sera of patients with DF contained higher levels of sIL-2R, sCD4, IL-2, and IFN gamma than the sera of healthy children (P less than 0.001 for sIL-2R, IL-2, and IFN gamma; P less than 0.05 for sCD4), but did not have elevated levels of sCD8. The levels of sIL-2R (P less than 0.05), sCD4 (P less than 0.001), and sCD8 (P less than 0.001) were higher in DHF than in DF on days 3-4 after the onset of fever. The levels of IL-2 and IFN gamma in patients with DHF were highest 1 d before defervescence. There were no significant differences in the levels of sIL-2R, sCD4, sCD8, IL-2, and IFN gamma among grades 1, 2, and 3 of DHF. These results indicate (a) T lymphocytes are activated and produce IL-2 and IFN gamma in vivo during DHF and DF, (b) CD4+ T lymphocytes are activated in DHF and DF, and the level of activation is higher in DHF than in DF, and (c) activation of CD8+ T lymphocytes is evident in DHF, but not in DF.
据报道，登革病毒感染的严重并发症登革出血热（DHF）在二次登革病毒感染期间比初次感染时更常见。为了阐明T淋巴细胞在DHF发病机制中的作用，我们试图通过检测59例DHF患者和41例登革热（DF）患者血清中可溶性白细胞介素-2受体（sIL-2R）、可溶性CD4（sCD4）、可溶性CD8（sCD8）、白细胞介素-2（IL-2）和干扰素-γ（IFNγ）的水平，来确定登革病毒感染期间T淋巴细胞在体内是否被激活。DHF患者急性血清中sIL-2R、sCD4、sCD8、IL-2和IFNγ的水平显著高于健康儿童血清（所有标志物P均小于0.001）。DF患者急性血清中sIL-2R、sCD4、IL-2和IFNγ的水平高于健康儿童血清（sIL-2R、IL-2和IFNγ的P小于0.001；sCD4的P小于0.05），但sCD8水平未升高。发热后第3 - 4天，DHF患者的sIL-2R（P小于0.05）、sCD4（P小于0.001）和sCD8（P小于0.001）水平高于DF患者。DHF患者的IL-2和IFNγ水平在退热前1天最高。DHF 1、2和3级患者的sIL-2R、sCD4、sCD8、IL-2和IFNγ水平无显著差异。这些结果表明：（a）DHF和DF期间T淋巴细胞在体内被激活并产生IL-2和IFNγ；（b）DHF和DF中CD4 + T淋巴细胞被激活，且DHF中的激活水平高于DF；（c）DHF中CD8 + T淋巴细胞激活明显，而DF中不明显。
