Induction of HIF-1α and the glycolytic pathway alters apoptotic and differentiation profiles of activated human T cells

Journal of Leukocyte Biology

Henning Zelba¹  Anis Larbi¹  David Goldeck¹  Graham Pawelec¹ 

[1] Center for Medical Research (ZMF), Tübingen Aging and Tumor Immunology Group (Sektion für Transplantationsimmunologie und Immunhämatologie), Tübingen, Germany Center for Medical Research (ZMF), Tübingen Aging and Tumor Immunology Group (Sektion für Transplantationsimmunologie und Immunhämatologie), Tübingen, Germany Center for Medical Research (ZMF), Tübingen Aging and Tumor Immunology Group (Sektion für Transplantationsimmunologie und Immunhämatologie), Tübingen, Germany

关键词: activation;    oxygen;    proliferation;    flow cytometry;   

DOI  :  10.1189/jlb.0509304

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

The majority of in vitro studies involving lymphocytes is performed in AtmO2, and the PhysO2 that T cells encounter are variable but commonly much lower. Previous studies showed changed kinetics and delayed proliferation of human T cells at PhysO2. Here, we show that CD3/CD28-dependent T cell activation induces faster cell cycling at AtmO2 than at PhysO2 (here taken to be 2%). Concomitantly with HIF-1α expression, we observed a switch in the T cell respiratory pathway toward glycolysis at PhysO2. Thus, modulating available glucose levels showed that at PhysO2, T cells rely more on glycolysis, associated with a higher phosphorylation of Aktser473. Although no difference in spontaneous apoptosis of resting cells was detected, it was increased significantly at PhysO2 after T cell activation and was different within the different T cell subsets. This may explain at least partly the differently altered proliferation and subset distribution observed in CD4+ and CD8+ T cells as a result of differences in naïve and memory subset distribution. Together, these findings suggest that T cell activation thresholds, subsequent proliferative capacity, and susceptibility to apoptosis, hitherto studied in air and thought to be crucial for monitoring immune responsiveness, may require re-assessment.

【 授权许可】

Unknown