DETECTION OF 3 DISTINCT PATTERNS OF T-HELPER CELL DYSFUNCTION IN ASYMPTOMATIC, HUMAN IMMUNODEFICIENCY VIRUS-SEROPOSITIVE PATIENTS - INDEPENDENCE OF CD4+ CELL NUMBERS AND CLINICAL STAGING
DETECTION OF 3 DISTINCT PATTERNS OF T-HELPER CELL DYSFUNCTION IN ASYMPTOMATIC, HUMAN IMMUNODEFICIENCY VIRUS-SEROPOSITIVE PATIENTS - INDEPENDENCE OF CD4+ CELL NUMBERS AND CLINICAL STAGING
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DOI：
10.1172/jci114376
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发表时间：
1989-12-01
影响因子：
15.9
通讯作者：
SHEARER, GM
中科院分区：
文献类型：
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作者：
CLERICI, M;STOCKS, NI;SHEARER, GM
我们已经测试了T辅助细胞（TH）的潜力，无症状，HIV血清阳性（HIV+）患者，使用体外测定IL-2的生产。用甲型流感病毒（FLU）、破伤风类毒素（泰特）、HLA同种抗原（ALLO）或PHA刺激74例HIV阳性患者和70例HIV阴性对照者的外周血白细胞（PBL），检测TH功能。在HIV阳性患者中，观察到四种不同的反应模式：（a）对所有四种刺激都有反应的患者（16%）;（B）对FLU和泰特选择性无反应，但对ALLO和PHA有反应的患者（54%）;（c）对FLU、泰特或ALLO无反应，但对PHA有反应的患者（16%）;以及（d）对这些刺激没有反应的患者（14%）。我们的研究结果表明，从对所有四种刺激都有反应的阶段到对任何测试刺激都没有反应的阶段的时间依赖性进展，以上述顺序进展。最早的TH缺陷是对FLU和泰特的反应丧失，表明CD 4 + MHC自限制性TH功能的选择性缺陷。ALLO和PHA IL-2应答的后期丧失表明涉及CD 4+和CD 8 + T细胞的更严重的TH功能障碍。无症状HIV+个体的TH无反应性模式与CD 4+细胞数量无关，也与Walter Reed分期标准无关。这项研究表明，在体外TH测定可以检测多个阶段的免疫失调早期的HIV感染过程中，并提出了可能性，分期的HIV+患者应包括在体外TH功能分析的类型这里描述的。
We have tested the T helper cell (TH) potential of asymptomatic, HIV seropositive (HIV+) patients, using an in vitro assay for IL-2 production. Peripheral blood leukocytes (PBL) from 74 HIV+ patients and 70 HIV- control donors were tested for TH function when stimulated with influenza A virus (FLU), tetanus toxoid (TET), HLA alloantigens (ALLO), or PHA. Of the HIV+ patients, four different response patterns were observed: (a) patients who responded to all four stimuli (16%); (b) patients who were selectively unresponsive to FLU and TET, but responded to ALLO and PHA (54%); (c) patients who were unresponsive to FLU, TET, or ALLO, but responsive to PHA (16%); and (d) patients who failed to respond to any of these stimuli (14%). Our results indicate a time-dependent progression from a stage responsive to all four stimuli to a stage unresponsive to any of the stimuli tested, progressing in the order outlined above. The earliest TH defect is the loss of responses to FLU and TET, indicating a selective defect in CD4+ MHC self-restricted TH function. The later loss of ALLO and PHA IL-2 responses suggests more severe TH dysfunction involving both CD4+ and CD8+ T cells. None of these patterns of TH unresponsiveness in asymptomatic HIV+ individuals were correlated with CD4+ cell numbers nor with Walter Reed staging criteria. This study indicates that the in vitro TH assay used can detect multiple stages of immune dysregulation early in the course of HIV infection and raises the possibility that staging of HIV+ patients should include in vitro TH functional analyses of the type described here.