Tamarit Amparo, Alberola Juan, Mira Josep Vicent, Tornero Carlos, Galindo María José, Navarro David
Department of Microbiology, School of Medicine, University of Valencia, Valencia, Spain.
J Med Virol. 2004 Nov;74(3):382-9. doi: 10.1002/jmv.20191.
T cell immunity to human cytomegalovirus (HCMV) was assessed in HAART-treated HIV-1 infected patients (9 asymptomatic, CDC group A; and 22 symptomatic, CDC group B), and in eight HIV-1 long term non-progressors. Patients were either prospectively or cross-sectionally examined for CD4(+) T cell counts, HIV RNA load, HCMV leukoDNAemia, HCMV DNA in urine, lymphoproliferative response (LPR) to HCMV and phytohemagglutinin (PHA), and cytokine secretion (IFN-gamma and IL-4) by HCMV-stimulated peripheral blood mononuclear cell (PBMC) cultures. No patient either progressed to clinical AIDS or developed HCMV active infection during the study period. Twenty-nine patients responded to HAART, though 12 patients failed to recover the LPR to HCMV over the study period (three from CDC group A and nine from CDC group B). In contrast to healthy control individuals, most patients displaying positive LPRs LPRs to HCMV had unstable responses. Sustained LPRs to HCMV were significantly associated with high pre-HAART nadir CD4(+) T cell counts. Long-term suppression of HIV viremia correlated with recovery of LPR to HCMV. Sequential PBMC cultures from most patients secreted IFN-gamma (but not IL-4) at normal levels upon HCMV stimulation, irrespective of the pre-HAART nadir CD4(+) T cell counts and CDC group to which patients belonged. Failure to reconstitute IFN-gamma response was associated with very low pre-HAART nadir CD4(+) T cell counts. Control of HCMV infection in the cohort was associated with either recovery or maintenance of IFN-gamma response rather than with reconstitution of LPR to HCMV. A LPR to HCMV was absent in three out of eight long term non-progressors; contrarily, all patients showed preserved IFN-gamma responses.
在接受高效抗逆转录病毒治疗(HAART)的HIV-1感染患者(9名无症状,疾病控制与预防中心A组;22名有症状,疾病控制与预防中心B组)以及8名HIV-1长期不进展者中评估了针对人巨细胞病毒(HCMV)的T细胞免疫。对患者进行前瞻性或横断面检查,检测其CD4(+) T细胞计数、HIV RNA载量、HCMV白细胞DNA血症、尿液中的HCMV DNA、对HCMV和植物血凝素(PHA)的淋巴细胞增殖反应(LPR)以及HCMV刺激的外周血单个核细胞(PBMC)培养物中的细胞因子分泌(IFN-γ和IL-4)。在研究期间,没有患者进展为临床艾滋病或发生HCMV活动性感染。29名患者对HAART有反应,不过在研究期间有12名患者未能恢复对HCMV的LPR(3名来自疾病控制与预防中心A组,9名来自疾病控制与预防中心B组)。与健康对照个体相比,大多数对HCMV显示阳性LPR的患者反应不稳定。对HCMV持续的LPR与HAART治疗前最低点CD4(+) T细胞计数高显著相关。HIV病毒血症的长期抑制与对HCMV的LPR恢复相关。大多数患者的连续PBMC培养物在HCMV刺激后以正常水平分泌IFN-γ(而非IL-4),无论患者的HAART治疗前最低点CD4(+) T细胞计数以及所属的疾病控制与预防中心组如何。未能重建IFN-γ反应与HAART治疗前最低点CD4(+) T细胞计数极低有关。该队列中HCMV感染的控制与IFN-γ反应的恢复或维持有关,而非与对HCMV的LPR重建有关。8名长期不进展者中有3名对HCMV无LPR;相反,所有患者均显示IFN-γ反应保留。