Immunologic Failure Despite Suppressive Antiretroviral Therapy Is Related to Activation and Turnover of Memory CD4 Cells
Immunologic Failure Despite Suppressive Antiretroviral Therapy Is Related to Activation and Turnover of Memory CD4 Cells
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DOI：
10.1093/infdis/jir507
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发表时间：
2011-10-15
影响因子：
6.4
通讯作者：
Rodriguez, Benigno
中科院分区：
文献类型：
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作者：
Lederman, Michael M.;Calabrese, Leonard;Rodriguez, Benigno
背景尽管进行了有效的抗逆转录病毒治疗，但CD 4（+）T细胞数量仍不能正常化是人类免疫缺陷病毒（HIV）感染的一个重要问题。为了评估这种情况下免疫失败的潜在决定因素，我们对HIV抑制后免疫失败的患者、治疗后CD 4（+）T细胞恢复的患者和健康对照者进行了全面的免疫表型表征。在免疫失败中发现所有CD 4（+）T细胞成熟亚群的严重耗竭和初始CD 8（+）T细胞的耗竭，这意味着T细胞产生/扩增的失败。在免疫失败时，CD 4（+）和CD 8（+）细胞都被激活，但只有记忆CD 4（+）细胞以增加的频率循环。这可能是体内暴露于微生物制品诱导的炎症的结果，因为内毒素受体CD 14（+）和白细胞介素6的可溶性水平在免疫失败中升高。在多变量分析中，初始T细胞耗竭、表型活化（CD 38（+）和HLA-DR表达）、记忆性CD 4（+）T细胞循环和可溶性CD 14（sCD 14）水平可区分免疫失败和免疫成功，即使调整了CD 4（+）T细胞最低值、治疗开始时的年龄和其他临床指标。免疫激活似乎与暴露于微生物元素有关，这区分了治疗HIV感染的免疫失败和免疫成功。
Background. Failure to normalize CD4(+) T-cell numbers despite effective antiretroviral therapy is an important problem in human immunodeficiency virus (HIV) infection.Methods. To evaluate potential determinants of immune failure in this setting, we performed a comprehensive immunophenotypic characterization of patients with immune failure despite HIV suppression, persons who experienced CD4(+) T-cell restoration with therapy, and healthy controls.Results. Profound depletion of all CD4(+) T-cell maturation subsets and depletion of naive CD8(+) T cells was found in immune failure, implying failure of T-cell production/expansion. In immune failure, both CD4(+) and CD8(+) cells were activated but only memory CD4(+) cells were cycling at increased frequency. This may be the consequence of inflammation induced by in vivo exposure to microbial products, as soluble levels of the endotoxin receptor CD14(+) and interleukin 6 were elevated in immune failure. In multivariate analyses, naive T-cell depletion, phenotypic activation (CD38(+) and HLA-DR expression), cycling of memory CD4(+) T cells, and levels of soluble CD14 (sCD14) distinguished immune failure from immune success, even when adjusted for CD4(+) T-cell nadir, age at treatment initiation, and other clinical indices.Conclusions. Immune activation that appears related to exposure to microbial elements distinguishes immune failure from immune success in treated HIV infection.