Scott Zachary A, Beaumier Coreen M, Sharkey Mark, Stevenson Mario, Luzuriaga Katherine
Graduate Program in Immunology/Virology and Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA 01605, USA.
J Immunol. 2003 Jun 1;170(11):5786-92. doi: 10.4049/jimmunol.170.11.5786.
This study investigated the relationship between HIV-1 replication and virus (HIV-1; CMV)-specific CD4(+) T cell frequency and function in HIV-1-infected children. HIV-1 gag p55-specific CD4(+) T cell IFN-gamma responses were detected in the majority of children studied. p55-specific responses were detected less commonly and at lower frequencies in children with <50 copies/ml plasma HIV-1 RNA than in children with active HIV-1 replication. In children with <50 copies/ml plasma HIV-1, p55-specific responses were detected only in children with evidence of ongoing HIV-1 replication, indicating a direct relationship between HIV-1 replication and HIV-specific CD4(+) T cell frequencies. In contrast, p55-specific proliferative responses were detected more frequently in children with <50 copies/ml plasma HIV-1. CMV-specific CD4(+) responses were more commonly detected and at higher frequencies in CMV-coinfected children with suppressed HIV-1 replication. The lack of HIV-specific CD4(+) proliferative responses, along with the preservation of CMV-specific CD4(+) responses in children with controlled HIV-1 replication, suggests that viral replication may have deleterious effects on HIV-1 and other virus-specific CD4(+) responses. Vaccination to stimulate HIV-specific CD4(+) T cell responses in these children may synergize with antiretroviral therapy to improve the long-term control of viral replication, and may perhaps allow the eventual discontinuation of antiretroviral therapy.
本研究调查了HIV-1感染儿童中HIV-1复制与病毒（HIV-1；巨细胞病毒）特异性CD4(+) T细胞频率及功能之间的关系。在大多数研究儿童中检测到了HIV-1 gag p55特异性CD4(+) T细胞的IFN-γ反应。与有活跃HIV-1复制的儿童相比，血浆HIV-1 RNA <50拷贝/ml的儿童中，p55特异性反应的检测频率较低且不常见。在血浆HIV-1 <50拷贝/ml的儿童中，仅在有持续HIV-1复制证据的儿童中检测到p55特异性反应，这表明HIV-1复制与HIV特异性CD4(+) T细胞频率之间存在直接关系。相比之下，血浆HIV-1 <50拷贝/ml的儿童中p55特异性增殖反应的检测频率更高。在HIV-1复制受抑制的巨细胞病毒合并感染儿童中，巨细胞病毒特异性CD4(+)反应的检测更为常见且频率更高。在HIV-1复制得到控制的儿童中，缺乏HIV特异性CD4(+)增殖反应以及巨细胞病毒特异性CD4(+)反应的保留，表明病毒复制可能对HIV-1和其他病毒特异性CD4(+)反应产生有害影响。在这些儿童中接种疫苗以刺激HIV特异性CD4(+) T细胞反应可能与抗逆转录病毒疗法协同作用，以改善对病毒复制的长期控制，并且可能最终允许停用抗逆转录病毒疗法。
