Bansal Anju, Gough Ethan, Sabbaj Steffanie, Ritter Doug, Yusim Karina, Sfakianos Greg, Aldrovandi Grace, Kaslow Richard A, Wilson Craig M, Mulligan Mark J, Kilby J Michael, Goepfert Paul A
Department of Medicine, University of Alabama at Birmingham, 20th Street South, Birmingham, AL 35294, USA.
AIDS. 2005 Feb 18;19(3):241-50.
To understand the mechanisms underlying the differential targeting of T-cell responses during HIV-1 disease progression.
We performed a cross-sectional analysis of HIV specific CD8 T-cell responses in peripheral blood mononuclear cells (PBMC) obtained from 21 subjects with well characterized acute or early infection and 88 subjects with chronic HIV-1 infection. We also performed a longitudinal analysis of T-cell responses in five early infected subjects one of whom was studied extensively over a 4-year-period.
PBMC were stimulated with pools of peptides encompassing all of the HIV-1 proteins in an interferon-gamma ELISpot assay. A mean entropy score was calculated for each peptide in the HIV-1 genome.
The early infected group preferentially targeted variable peptides with higher entropy while responses towards more conserved peptides with lower entropy predominated in the group with chronic infection. In five early infected subjects followed longitudinally, responses to variable proteins declined while those to conserved proteins increased over time. In the subject who was followed for 4 years, epitopes in Vif and Nef were targeted early and escape occurred in three of these four epitopes. During the chronic phase of his infection, the early responses waned with an associated increase in breadth of T-cell responses mainly to Gag and Pol epitopes.
Taken together, these data demonstrate that HIV-specific CD8 T cells are directed preferentially to the variable peptides in early infection but diminish in frequency during chronic disease, in large part due to cytotoxic T lymphocyte escape.
了解HIV-1疾病进展过程中T细胞反应差异靶向的潜在机制。
我们对从21名具有明确特征的急性或早期感染受试者以及88名慢性HIV-1感染受试者获得的外周血单核细胞（PBMC）中的HIV特异性CD8 T细胞反应进行了横断面分析。我们还对5名早期感染受试者的T细胞反应进行了纵向分析，其中一名受试者在4年期间进行了广泛研究。
在干扰素-γ ELISpot试验中，用包含所有HIV-1蛋白的肽池刺激PBMC。计算HIV-1基因组中每个肽的平均熵得分。
早期感染组优先靶向具有较高熵的可变肽，而慢性感染组中对具有较低熵的更保守肽的反应占主导。在纵向随访的5名早期感染受试者中，对可变蛋白的反应随时间下降，而对保守蛋白的反应增加。在随访4年的受试者中，Vif和Nef中的表位早期被靶向，这四个表位中有三个发生了逃逸。在其感染的慢性期，早期反应减弱，同时T细胞反应广度主要对Gag和Pol表位的反应增加。
综上所述，这些数据表明，HIV特异性CD8 T细胞在早期感染时优先靶向可变肽，但在慢性疾病期间频率降低，这在很大程度上是由于细胞毒性T淋巴细胞逃逸。
