Determination of antigen-specific: Memory/effector CD4+ T cell frequencies by flow cytometry - Evidence for a novel, antigen-specific homeostatic mechanism in HIV-associated immunodeficiency
Determination of antigen-specific: Memory/effector CD4+ T cell frequencies by flow cytometry - Evidence for a novel, antigen-specific homeostatic mechanism in HIV-associated immunodeficiency
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DOI：
10.1172/jci119338
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发表时间：
1997-04-01
影响因子：
15.9
通讯作者：
Picker, LJ
中科院分区：
文献类型：
--
作者：
Waldrop, SL;Pitcher, CJ;Picker, LJ
由CD 4 + T细胞高度调节的效应细胞因子分泌在针对病原体如巨细胞病毒的免疫保护中起关键作用。在这里，我们直接比较的频率和功能特性的巨细胞病毒特异性CD 4+记忆/效应T细胞在正常和HIV+受试者使用一种新的，高效的多参数流式细胞术检测细胞因子（S）的细胞内积累后，短期（6小时）在体外抗原刺激。该测定中的反应与致敏史的独立测量值精确相关（例如，血清反应性），并允许同时评估单个效应T细胞中的多种细胞因子。健康HIV个体表现出平均0.71、0.72、0.38和0.06%的CD 4 + T细胞分别对巨细胞病毒产生γ-IFN、TNF-α、IL-2和IL-4应答，同时产生γ-IFN、TNF-α、IL-2是最常见的效应子表型。值得注意的是，在40%的HIV+受试者中，总体巨细胞病毒特异性CD 4+效应子频率显著较高（2.7-8.0%），并表现出主要极化的γ-IFN +/TNF-α +/IL-2-/IL-4-表型。相反，在HIV+组中，异源、非普遍存在的病毒（如腮腺炎病毒）的CD 4+效应子频率较低或不存在。这些数据表明，HIV疾病中存在稳态机制，该机制选择性地保留与普遍存在的病原体（如巨细胞病毒）反应的记忆T细胞群，可能以T细胞记忆为代价，以更零星地遇到感染性病原体。
The highly regulated secretion of effector cytokines by CD4+ T cells plays a critical role in immune protection against pathogens such as cytomegalovirus. Here, we directly compare the frequency and functional characteristics of cytomegalovirus-specific CD4+ memory/effector T cells in normal and HIV+ subjects using a novel, highly efficient multiparameter flow cytometric assay that detects the rapid intracellular accumulation of cytokine(s) after short-term (6 h) in vitro antigen stimulation. Responses in this assay correlate precisely with independent measures of sensitization history (e.g., seroreactivity), and allow the simultaneous assessment of multiple cytokines in single effector T cells, Healthy HIV- individuals manifested an average of 0.71, 0.72, 0.38, and 0.06% CD4+ T cells responding to cytomegalovirus with gamma-IFN, TNF-alpha, IL-2, and IL-4 production, respectively, with the simultaneous production of gamma-IFN, TNF-alpha, and IL-2 being the most common effector phenotype. Significantly, overall cytomegalovirus-specific CD4+ effector frequencies were markedly higher among 40% of HIV+ subjects (2.7-8.0%), and demonstrated a predominately polarized gamma-IFN+/TNF-alpha+/IL-2-/IL-4- phenotype, In contrast, CD4+ effector frequencies for heterologous, nonubiquitous viruses such as the mumps virus were low or absent in the HIV+ group. These data suggest the existence of homeostatic mechanisms in HIV disease that selectively preserve memory T cell populations reactive with ubiquitous pathogens such as cytomegalovirus-likely at the expense of T cell memory to more sporadically encountered infectious agents.