Red blood cells upregulate cytoprotective proteins and the labile iron pool in dividing human T cells despite a reduction in oxidative stress

• Published in: Free radical biology & medicine 2003-12, Vol.35 (11), p.1404-1416
• Main Authors: Fonseca, Ana Mafalda, Pereira, Carlos F, Porto, Graça, Arosa, Fernando A
• Format: Article
• Language: English
• Subjects: Antigens, CD - metabolism; Antigens, Differentiation, B-Lymphocyte - metabolism; Apoptosis; Blotting, Western; Cell Survival; Cells, Cultured; Erythrocytes - metabolism; Ferritin; Ferritins - chemistry; Ferritins - metabolism; Flow Cytometry; Free Radicals; Growth; Heme - chemistry; Heme oxygenase; Heme Oxygenase (Decyclizing) - metabolism; Heme Oxygenase-1; Humans; Iron; Iron - chemistry; Iron - metabolism; Membrane Proteins; Oxidation-Reduction; Oxidative Stress; Precipitin Tests; Reactive Oxygen Species; Receptors, Transferrin - metabolism; Red blood cells; Survival; T cells; T-Lymphocytes - metabolism; Time Factors; Transferrin receptor; Up-Regulation
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2003.08.011

We have recently reported that red blood cells (RBC) promote T cell growth and survival by inhibiting activation-induced T cell death. In the present study, we have examined parameters of oxidative stress and intracellular iron in activated T cells and correlated these data with the expression of ferritin, heme oxygenase-1 (HO-1), and the transferrin receptor CD71. T cells growing in the presence of RBC had reduced levels of reactive oxygen species (ROS) and oxidatively modified proteins, suggesting that RBC efficiently counteracted ROS production on the activated T cells. Flow cytometry and immunodetection demonstrated that T cells dividing in the presence of RBC had increased levels of intracellular ferritin rich in L-subunits and HO-1 along with a downmodulation in CD71 expression. Finally, using the fluorescent iron indicator calcein and flow cytometry analysis, we were able to show that a relative amount of the labile iron pool (LIP) was upregulated in T cells growing in the presence of RBC. These findings are consistent with a typical response to iron overload. However, neither heme compounds nor ferric iron reproduced the levels of expansion and survival of T cells induced by intact RBC. Altogether, these data suggest that RBC inhibit apoptosis of activated T cells by a combination of ROS scavenging and upregulation of cytoprotective proteins such as ferritin and HO-1, which may counteract a possible toxic effect of the increased intracellular free iron.