Rodriguez Benigno, Lederman Michael M, Jiang Wei, Bazdar Douglas A, Gàrate Kristen, Harding Clifford V, Sieg Scott F
Division of Infectious Diseases, Case Western Reserve University, Center foe AIDS Research, University Hospitals of Cleveland, Cleveland, Ohio, USA.
AIDS. 2006 Jun 26;20(10):1379-89. doi: 10.1097/01.aids.0000233571.51899.ab.
To examine the effects of interferon-alpha (IFN-alpha) on T cell survival and activation in HIV infection.
The effects of IFN-alpha on spontaneous apoptosis and CD38 expression among T cell subsets were determined in vitro and studied in relation to CD4 cell counts, plasma HIV RNA levels and the age of the subjects.
Peripheral blood mononuclear cells from 48 HIV-infected persons and 17 healthy donors were incubated in vitro overnight with or without the addition of IFN-alpha. Percentages of apoptotic cells (positive for annexin V) and CD38 cells were determined among T cell subsets.
IFN-alpha inhibited spontaneous apoptosis of CD4 and CD8 T lymphocytes. This protective activity was impaired in CD4 T cells from HIV-infected persons. The reduced protection of IFN-alpha among CD4 cells from HIV-infected persons was not related to the percentages of activated (CD38 or CD45RO+CD38+) cells. Surprisingly, IFN-alpha induced CD38 expression among CD8 T cells from HIV-infected persons, and the magnitude of this effect was directly related to circulating CD4 T cell count. The CD8 T cell subset that expressed CD38 in response to IFN-alpha was defined as CD28 negative, CD62 ligand (CD62L) intermediate/negative.
Heightened expression of IFN-alpha in HIV infection may contribute to the phenotypic activation state that characterizes chronic infection while a diminished responsiveness of CD4 T cells to the protective effect of this cytokine may contribute to differential survival of CD4 and CD8 T cells in HIV disease.
研究α干扰素（IFN-α）对HIV感染中T细胞存活及激活的影响。
在体外确定IFN-α对T细胞亚群中自发凋亡及CD38表达的影响，并结合CD4细胞计数、血浆HIV RNA水平及受试者年龄进行研究。
将48例HIV感染者及17例健康供者的外周血单个核细胞在体外培养过夜，分别添加或不添加IFN-α。测定T细胞亚群中凋亡细胞（膜联蛋白V阳性）及CD38细胞的百分比。
IFN-α抑制CD4和CD8 T淋巴细胞的自发凋亡。HIV感染者CD4 T细胞中的这种保护活性受损。HIV感染者CD4细胞中IFN-α保护作用的降低与活化细胞（CD38或CD45RO+CD38+）的百分比无关。令人惊讶的是，IFN-α诱导HIV感染者CD8 T细胞中CD38表达，且这种效应的程度与循环CD4 T细胞计数直接相关。对IFN-α产生反应而表达CD38的CD8 T细胞亚群定义为CD28阴性、CD62配体（CD62L）中等/阴性。
HIV感染中IFN-α表达升高可能导致慢性感染特征性的表型激活状态，而CD4 T细胞对这种细胞因子保护作用的反应性降低可能导致HIV疾病中CD4和CD8 T细胞的不同存活情况。
