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Originally published online as doi:10.1189/jlb.0509304 on November 5, 2009

Published online before print November 5, 2009
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(Journal of Leukocyte Biology. 2010;87:265-273.)
© 2010 Society for Leukocyte Biology

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

Anis Larbi1, Henning Zelba, David Goldeck and Graham Pawelec

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

1. Correspondence: Center for Medical Research (ZMF), Tübingen Aging and Tumor Immunology Group (Sektion für Transplantationsimmunologie und Immunhämatologie), Waldhörnlestrasse 22, 72072 Tübingen, Germany. E-mail: anis.larbi{at}medizin.uni-tuebingen.de

ABSTRACT

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-1{alpha} 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.

Key Words: activation • oxygen • proliferation • flow cytometry