Teixeira L, Valdez H, McCune J M, Koup R A, Badley A D, Hellerstein M K, Napolitano L A, Douek D C, Mbisa G, Deeks S, Harris J M, Barbour J D, Gross B H, Francis I R, Halvorsen R, Asaad R, Lederman M M
Division of Infectious Diseases and the Center for AIDS Research, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Ohio 44106, USA.
AIDS. 2001 Sep 28;15(14):1749-56. doi: 10.1097/00002030-200109280-00002.
To characterize immune phenotype and thymic function in HIV-1-infected adults with excellent virologic and poor immunologic responses to highly active antiretroviral therapy (HAART).
Cross-sectional study of patients with CD4 T cell rises of > or = 200 x 10(6) cells/l (CD4 responders; n = 10) or < 100 x 10(6) cells/l (poor responders; n = 12) in the first year of therapy.
Poor responders were older than CD4 responders (46 versus 38 years; P < 0.01) and, before HAART, had higher CD4 cell counts (170 versus 35 x 106 cells/l; P = 0.11) and CD8 cell counts (780 versus 536 x 10(6) cells/l; P = 0.02). After a median of 160 weeks of therapy, CD4 responders had more circulating naive phenotype (CD45+CD62L+) CD4 cells (227 versus 44 x 10(6) cells/l; P = 0.001) and naive phenotype CD8 cells (487 versus 174 x 10(6) cells/l; P = 0.004) than did poor responders (after 130 weeks). Computed tomographic scans showed minimal thymic tissue in 11/12 poor responders and abundant tissue in 7/10 responders (P = 0.006). Poor responders had fewer CD4 cells containing T cell receptor excision circles (TREC) compared with CD4 responders (2.12 versus 27.5 x 10(6) cells/l; P = 0.004) and had shorter telomeres in CD4 cells (3.8 versus 5.3 kb; P = 0.05). Metabolic labeling studies with deuterated glucose indicated that the lower frequency of TREC-containing lymphocytes in poor responders was not caused by accelerated proliferation kinetics.
Poor CD4 T cell increases observed in some patients with good virologic response to HAART may be caused by failure of thymic T cell production.
对高效抗逆转录病毒疗法（HAART）治疗后病毒学反应良好但免疫反应不佳的HIV-1感染成年患者的免疫表型和胸腺功能进行特征描述。
对治疗第一年CD4 T细胞计数升高≥200×10⁶细胞/升的患者（CD4反应者；n = 10）或＜100×10⁶细胞/升的患者（反应不佳者；n = 12）进行横断面研究。
反应不佳者比CD4反应者年龄更大（46岁对38岁；P＜0.01），在接受HAART之前，其CD4细胞计数更高（170对35×10⁶细胞/升；P = 0.11），CD8细胞计数也更高（780对536×10⁶细胞/升；P = 0.02）。经过中位160周的治疗后，CD4反应者比反应不佳者（130周后）有更多循环中的幼稚表型（CD45⁺CD62L⁺）CD4细胞（227对44×10⁶细胞/升；P = 0.001）和幼稚表型CD8细胞（487对174×10⁶细胞/升；P = 0.004）。计算机断层扫描显示，12名反应不佳者中有11名胸腺组织极少，10名反应者中有7名胸腺组织丰富（P = 0.006）。与CD4反应者相比，反应不佳者含有T细胞受体切除环（TREC）的CD4细胞更少（2.12对27.5×10⁶细胞/升；P = 0.004），且CD4细胞中的端粒更短（3.8对5.3 kb；P = 0.05）。用氘代葡萄糖进行的代谢标记研究表明，反应不佳者中含TREC淋巴细胞频率较低并非由增殖动力学加速所致。
在一些对HAART病毒学反应良好的患者中观察到的CD4 T细胞增加不佳可能是胸腺T细胞生成失败所致。
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