Increased glucose metabolic activity is associated with CD4+ T-cell activation and depletion during chronic HIV infection

葡萄糖代谢活性增加与慢性 HIV 感染期间 CD4+ T 细胞活化和耗竭有关

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作者:Clovis S Palmer, Matias Ostrowski, Maelenn Gouillou, Louis Tsai, Di Yu, Jingling Zhou, Darren C Henstridge, Anna Maisa, Anna C Hearps, Sharon R Lewin, Alan Landay, Anthony Jaworowski, Joseph M McCune, Suzanne M Crowe

Conclusion

Our data suggest that Glut1 is a potentially novel and functional marker of CD4 T-cell activation during HIV infection. In addition, Glut1 expression on CD4 T cells may be exploited as a prognostic marker for CD4 T-cell loss during HIV disease progression.

Methods

Thirty-eight HIV-infected treatment-naive, 35 HIV+/combination antiretroviral therapy, seven HIV+ long-term nonprogressors and 25 HIV control individuals were studied. Basal markers of glycolysis [e.g. glucose transporter-1 (Glut1) expression, glucose uptake, intracellular glucose-6-phosphate, and L-lactate] were measured in T cells. The cellular markers of immune activation, CD38 and HLA-DR, were measured by flow cytometry.

Results

The surface expression of the Glut1 is up-regulated in CD4 T cells in HIV-infected patients compared with uninfected controls. The percentage of circulating CD4Glut1 T cells was significantly increased in HIV-infected patients and was not restored to normal levels following combination antiretroviral therapy. Basal markers of glycolysis were significantly higher in CD4Glut1 T cells compared to CD4Glut1 T cells. The proportion of CD4Glut1 T cells correlated positively with the expression of the cellular activation marker, HLA-DR, on total CD4 T cells, but inversely with the absolute CD4 T-cell count irrespective of HIV treatment status.

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