Relationship between T cell activation and CD4+ T cell count in HIV-seropositive individuals with undetectable plasma HIV RNA levels in the absence of therapy
Relationship between T cell activation and CD4+ T cell count in HIV-seropositive individuals with undetectable plasma HIV RNA levels in the absence of therapy
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DOI：
10.1086/524143
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发表时间：
2008-01-01
影响因子：
6.4
通讯作者：
Deeks, Steven G.
中科院分区：
文献类型：
--
作者：
Hunt, Peter W.;Brenchley, Jason;Deeks, Steven G.
背景资料。虽然未经治疗的人类免疫缺陷病毒(HIV)感染患者保持无法检测到的血浆HIV RNA水平(精英控制者)具有高的HIV特异性免疫反应，但尚不清楚他们是否经历了异常水平的T细胞激活，这可能导致免疫缺陷。我们比较了30名精英控制员、47名HIV非感染者、187名接受抗逆转录病毒治疗(抗逆转录病毒治疗被抑制)的HIV感染者和66名可检测到病毒血症的未经治疗的HIV感染者的激活(CD38(+)HLA-DR+)T细胞的百分比。由于在HIV感染中，细菌产物的粘膜易位可能有助于T细胞的激活，因此我们还检测了血浆脂多糖(LPS)水平。虽然对照组的CD4(+)细胞计数中位数为727个/mm(3)，但有3个(10%)的CD4(+)细胞计数为350个/mm(3)，2个(7%)患有获得性免疫缺陷综合征。控制组的CD4(+)和CD8(+)细胞激活水平高于HIV阴性受试者，CD8(+)细胞激活水平高于抑制的抗逆转录病毒治疗组(P=.048)。在对照组中，较高的CD4(+)和CD8(+)T细胞活性与较低的CD4(+)细胞计数相关(P=0.009和P=0.047)。控制组的内毒素水平高于HIV阴性的受试者(P=.001)，且控制组中较高的内毒素水平与较高的CD8(+)T细胞活性有关(P=.039)。HIV控制者有异常高的T细胞激活水平，这可能导致进行性的CD4(+)T细胞丧失，即使没有可测量的病毒血症。
Background. Although untreated human immunodeficiency virus (HIV)-infected patients maintaining undetectable plasma HIV RNA levels (elite controllers) have high HIV-specific immune responses, it is unclear whether they experience abnormal levels of T cell activation, potentially contributing to immunodeficiency.Methods. We compared percentages of activated (CD38(+) HLA-DR+) T cells between 30 elite controllers, 47 HIV-uninfected individuals, 187 HIV-infected individuals with undetectable viremia receiving antiretroviral therapy (antiretroviral therapy suppressed), and 66 untreated HIV-infected individuals with detectable viremia. Because mucosal translocation of bacterial products may contribute to T cell activation in HIV infection, we also measured plasma lipopolysaccharide (LPS) levels.Results. Although the median CD4(+) cell count in controllers was 727 cells/mm(3), 3 (10%) had CD4(+) cell counts < 350 cells/mm(3) and 2 (7%) had acquired immunodeficiency syndrome. Controllers had higher CD4(+) and CD8(+) cell activation levels (P < .001 for both) than HIV-negative subjects and higher CD8(+) cell activation levels than the antiretroviral therapy suppressed (P = .048). In controllers, higher CD4(+) and CD8(+) T cell activation was associated with lower CD4(+) cell counts (P = .009 and P = .047). Controllers had higher LPS levels than HIV-negative subjects (P = .001), and in controllers higher LPS level was associated with higher CD8(+) T cell activation (P = .039).Conclusion. HIV controllers have abnormally high T cell activation levels, which may contribute to progressive CD4(+) T cell loss even without measurable viremia.