Red blood cells inhibit activation-induced cell death and oxidative stress in human peripheral blood T lymphocytes.
Red blood cells (RBCs) are known to perform one prominent function: to carry and deliver oxygen to the tissues. Earlier studies, however, suggested a role for RBCs in potentiating T-cell proliferation in vitro. Here it is shown that the presence of RBCs in cultures of stimulated human peripheral blood lymphocytes strengthens T-cell proliferation and survival. Analysis of phosphatidylserine externalization and DNA fragmentation showed that RBCs inhibit T-cell apoptosis. This inhibition correlated with a reduction in CD71 but not CD95 expression. RBCs enhanced T-cell proliferation and survival upon activation with phytohemagglutinin and with OKT3 antibodies. Studies aimed at characterizing the cellular and molecular basis of the protection afforded to T cells by RBCs showed that (1) optimal protection required intact RBCs and red cell/T-cell contact but not monocytes; (2) RBCs markedly reduced the level of intracellular reactive oxygen species; and (3) RBCs inhibited the formation of protein-bound acrolein, a peroxidation adduct in biologic systems. Overall, these data indicate that human RBCs protect T cells from activation-induced cell death, at least in part by reducing the pro-oxidant state, and suggest a role for RBCs as conceivable modulators of T-cell homeostasis.
Fonseca
A M
AM
Laboratory of Molecular Immunology, Institute for Molecular and Cell Biology, University of Porto, Portugal.
Porto
G
G
Uchida
K
K
Arosa
F A
FA
D000171:Acrolein / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000032:analysis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D017209:Apoptosis; D002455:Cell Division; D002470:Cell Survival; D018920:Coculture Techniques; D053938:DNA Fragmentation; D004912:Erythrocytes / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D009000:Monocytes / Q000502:physiology; D018384:Oxidative Stress; D010718:Phosphatidylserines / Q000378:metabolism; D010835:Phytohemagglutinins / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D011990:Receptors, Transferrin; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D019014:fas Receptor / Q000032:analysis
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C068126:CD71 antigen; D010718:Phosphatidylserines; D010835:Phytohemagglutinins; D017382:Reactive Oxygen Species; D011990:Receptors, Transferrin; D019014:fas Receptor; D000171:Acrolein