Preserved central memory and activated effector memory CD4+ T-cell subsets in human immunodeficiency virus controllers:: An ANRS EP36 study
Preserved central memory and activated effector memory CD4+ T-cell subsets in human immunodeficiency virus controllers:: An ANRS EP36 study
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DOI：
10.1128/jvi.01401-07
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发表时间：
2007-12-01
影响因子：
5.4
通讯作者：
Chakrabarti, Lisa A.
中科院分区：
文献类型：
--
作者：
Potter, Simon J.;Lacabaratz, Christine;Chakrabarti, Lisa A.
人类免疫缺陷病毒（HIV）控制者是在没有抗逆转录病毒治疗的情况下自发控制HIV 1型复制10年或更长时间的罕见个体。在本研究中，HIV控制者（n = 11）尽管抗原负荷非常低，但仍保持了有效的HIV特异性CD 4应答。他们的CD 4（+）中央记忆T（T-CM）细胞的特征是接近正常的数量和保留的白细胞介素-2（IL-2）分泌，以响应HIV抗原和一致的高表达的生存受体IL-7受体α（IL-7 R α）。控制者表达CCR 7的水平高于未感染的对照组，表明T-CM细胞归巢模式的差异。在HIV控制者中，CD 4（+）效应记忆T（T-EM）细胞应答是多功能的，而在病毒血症患者中，IL-2分泌丧失。细胞因子的产生是控制者的三倍，而病毒载量检测不到的治疗患者，这表明前一组本质上更有效的反应。总的CD 4（+）T-EM细胞池在对照组中经历免疫活化，如HLA-DR表达增加、IL-7 R α表达减少、多克隆刺激后γ干扰素产生的偏向以及与慢性CCR 5下调相关的巨噬细胞炎性蛋白1 β分泌增加所示。因此，HIV控制者显示出保留的CD 4（+）T-EM细胞区室和CD 4（+）T-EM细胞区室中有效功能激活的迹象。虽然控制者没有表现出与疾病进展相关的全身免疫激活模式，但他们的免疫激活迹象仅限于效应区室。这些发现表明，诱导一个有效的，无害的免疫激活类型的患者自发控制艾滋病毒。
Human immunodeficiency virus (HIV) controllers are rare individuals who spontaneously control HIV type 1 replication for 10 years or more in the absence of antiretroviral treatment. In the present study, HIV controllers (n = 11) maintained potent HIV-specific CD4 responses in spite of very low antigenic loads. Their CD4(+) central memory T (T-CM) cells were characterized by near-normal numbers and preserved interleukin-2 (IL-2) secretion in response to HIV antigens and uniformly high expression of the survival receptor IL-7 receptor alpha (IL-7R alpha). Controllers expressed CCR7 at higher levels than uninfected controls, suggesting differences in T-CM-cell homing patterns. CD4(+) effector memory T (T-EM)-cell responses were polyfunctional in HIV controllers, while IL-2 secretion was lost in viremic patients. Cytokine production was three times higher in controllers than in treated patients with undetectable viral loads, suggesting an intrinsically more efficient response in the former group. The total CD4(+) T-EM-cell pool underwent immune activation in controllers, as indicated by increased HLA-DR expression, decreased IL-7R alpha expression, a bias towards gamma interferon production upon polyclonal stimulation, and increased macrophage inflammatory protein 1 beta secretion associated with chronic CCR5 down-regulation. Thus, HIV controllers showed a preserved CD4(+) T-EM-cell compartment and signs of potent functional activation in the CD4(+) T-EM-cell compartment. While controllers did not show the generalized immune activation pattern associated with disease progression, they had signs of immune activation restricted to the effector compartment. These findings suggest the induction of an efficient, nondetrimental type of immune activation in patients who spontaneously control HIV.