Feeney Margaret E, Draenert Rika, Roosevelt Kathleen A, Pelton Stephen I, McIntosh Kenneth, Burchett Sandra K, Mao Charlotte, Walker Bruce D, Goulder Philip J R
Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
J Immunol. 2003 Dec 15;171(12):6968-75. doi: 10.4049/jimmunol.171.12.6968.
Gag-specific CD4 proliferative responses correlate inversely with HIV-1 RNA levels in infected adults, and robust responses are characteristic of long-term nonprogressive infection. However, strong responses are seldom detected in adult subjects with progressive infection and are not generally reconstituted on highly active antiretroviral therapy (HAART). To date, the role of HIV-1-specific Th responses in children has not been thoroughly examined. We characterized Gag-specific CD4 responses among 35 perinatally infected subjects, including 2 children who spontaneously control viremia without antiretroviral therapy, 21 children with viral loads (VL) of <400 on HAART, and 12 viremic children. Gag-specific Th activity was assessed by lymphoproliferative assay, and responses were mapped using overlapping Gag peptides in an IFN-gamma ELISPOT. Robust proliferative responses were detected in the children exhibiting spontaneous control of viremia, and mapping of targeted Gag regions in one such subject identified multiple epitopes. Among children >or=5 years old, 14 of 17 subjects with VL of <400 on HAART demonstrated a significant p24 proliferative response (median p24 stimulation index, 20), in contrast with only 1 of 9 viremic children (median p24 stimulation index, 2.0; p = 0.0008). However, no subject younger than 5 years of age possessed a significant response, even when viremia was fully suppressed. When compared with adults with VL of <400 on HAART, Th responses among children with VL of <400 were both more frequent (p = 0.009) and of greater magnitude (p = 0.002). These data suggest that children may have a greater intrinsic capacity to reconstitute HIV-1-specific immunity than adults, and may be excellent candidates for immune-based therapies.
在受感染的成年人中，针对Gag的CD4增殖反应与HIV-1 RNA水平呈负相关，强烈反应是长期非进展性感染的特征。然而，在进行性感染的成年受试者中很少检测到强烈反应，并且在高效抗逆转录病毒治疗（HAART）中通常不会恢复。迄今为止，HIV-1特异性Th反应在儿童中的作用尚未得到充分研究。我们对35名围产期感染的受试者的Gag特异性CD4反应进行了特征分析，其中包括2名未经抗逆转录病毒治疗而自发控制病毒血症的儿童、21名接受HAART治疗且病毒载量（VL）<400的儿童以及12名病毒血症儿童。通过淋巴细胞增殖试验评估Gag特异性Th活性，并使用重叠的Gag肽在IFN-γ ELISPOT中绘制反应图谱。在表现出自发控制病毒血症的儿童中检测到强烈的增殖反应，并且在其中一名受试者中对靶向Gag区域的图谱分析确定了多个表位。在年龄≥5岁的儿童中，17名接受HAART治疗且VL<400的受试者中有14名表现出显著的p24增殖反应（p24刺激指数中位数为20），相比之下，9名病毒血症儿童中只有1名（p24刺激指数中位数为2.0；p = 0.0008）。然而，即使病毒血症得到完全抑制，没有一名5岁以下的受试者有显著反应。与接受HAART治疗且VL<400的成年人相比，VL<400的儿童中的Th反应更频繁（p = 0.009）且幅度更大（p = 0.002）。这些数据表明，儿童重建HIV-1特异性免疫的内在能力可能比成年人更强，并且可能是基于免疫疗法的优秀候选者。
