van Noesel C J, Gruters R A, Terpstra F G, Schellekens P T, van Lier R A, Miedema F
Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
J Clin Invest. 1990 Jul;86(1):293-9. doi: 10.1172/JCI114698.
In addition to a well-documented depletion of CD4+ T helper cells in later stages of human immunodeficiency virus (HIV) infection, evidence has been provided for a specific unresponsiveness to triggering either by specific antigen in the context of autologous major histocompatibility molecules (self + X) or anti-CD3 monoclonal antibodies (MAb) in both CD4 and CD8 cells from asymptomatic HIV-infected individuals. In the present study we analyzed this unresponsiveness using mitogenic antibodies to distinct T cell membrane receptors. T cells from HIV-infected men who had normal numbers of CD4+ T cells responded poorly to activation signals via the CD3 membrane antigen in both accessory cell-dependent as well as accessory cell-independent culture systems. A similar low response was observed in an anti-CD2-driven system. In contrast, proliferation induced by anti-CD3, anti-CD2, or the phorbol ester Phorbol myristate acetate could be normally enhanced by anti-CD28 MAb. We demonstrated that this unresponsiveness is not due to a failure to induce early events required for activation, such as increased intracellular concentration of free calcium and activation of protein kinase C, but is caused by an imbalance between naive and memory T cells. In HIV-infected asymptomatic men, CD29+ memory T cells are selectively depleted which results in a poor responsiveness to self + X. These findings provide new insights that may have implications for our understanding of the immunopathogenesis of AIDS.
除了在人类免疫缺陷病毒（HIV）感染后期有充分记录的CD4 + T辅助细胞耗竭外，已有证据表明，无症状HIV感染者的CD4和CD8细胞对自体主要组织相容性分子（自身+ X）背景下的特异性抗原或抗CD3单克隆抗体（MAb）触发均表现出特异性无反应性。在本研究中，我们使用针对不同T细胞膜受体的促有丝分裂抗体分析了这种无反应性。来自CD4 + T细胞数量正常的HIV感染男性的T细胞，在辅助细胞依赖性和辅助细胞非依赖性培养系统中，对通过CD3膜抗原的激活信号反应不佳。在抗CD2驱动的系统中也观察到类似的低反应性。相比之下，抗CD28单克隆抗体可正常增强抗CD3、抗CD2或佛波酯肉豆蔻酸佛波醇酯诱导的增殖。我们证明，这种无反应性不是由于未能诱导激活所需的早期事件，如细胞内游离钙浓度增加和蛋白激酶C激活，而是由幼稚T细胞和记忆T细胞之间的失衡引起的。在HIV感染的无症状男性中，CD29 +记忆T细胞被选择性消耗，这导致对自身+ X反应不佳。这些发现为我们理解艾滋病的免疫发病机制提供了新的见解。
