Cusick Matthew F, Libbey Jane E, Cox Gill Joan, Fujinami Robert S, Eckels David D
Department of Pathology, University of Utah School of Medicine, 30 North 1900 East, 3R330 SOM, Salt Lake City, UT 84132, USA.
Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI 53226, USA.
Future Virol. 2013 Jul;8(7). doi: 10.2217/fvl.13.49.
To determine whether modulation of T-cell responses by naturally occurring viral variants caused an increase in numbers of Tregs in HCV-infected patients.
PATIENTS MATERIALS & METHODS: Human peripheral blood mononuclear cells, having proliferative responses to a wild-type HCV-specific CD4 T-cell epitope, were used to quantify, via proliferative assays, flow cytometry and class II tetramers, the effects of naturally occurring viral variants arising in the immunodominant epitope.
In combination, the wild-type and variant peptides led to enhanced suppression of an anti-HCV T-cell response. The variant had a lower avidity for the wild-type-specific CD4 T cell. Variant-stimulated CD4 T cells had increased Foxp3, compared with wild-type-stimulated cells.
A stable viral variant from a chronic HCV subject was able to induce Tregs in multiple individuals that responded to the wild-type HCV-specific CD4 T-cell epitope.
确定天然存在的病毒变异体对T细胞反应的调节是否会导致丙型肝炎病毒(HCV)感染患者中调节性T细胞(Tregs)数量增加。
使用对野生型HCV特异性CD4 T细胞表位具有增殖反应的人外周血单个核细胞,通过增殖试验、流式细胞术和II类四聚体来量化免疫显性表位中天然存在的病毒变异体的影响。
野生型和变异体肽共同作用导致抗HCV T细胞反应的抑制增强。变异体对野生型特异性CD4 T细胞的亲和力较低。与野生型刺激的细胞相比,变异体刺激的CD4 T细胞中Foxp3增加。
来自慢性HCV患者的稳定病毒变异体能够在多个对野生型HCV特异性CD4 T细胞表位有反应的个体中诱导Tregs。