title: Red blood cells carry out T cell growth and survival bioactivities  that are sensitive to cyclosporine A.
abstract: Red blood cells (RBC) have emerged as a novel regulatory cell type endowed with bioactivities toward activated human T cells. Herein we show that the RBC bioactivities act on intracellular pathways initiated by T cell receptor (TCR)-dependent and -independent stimuli,including IL-2, IL-15, and the mixture of phorbol dibutyrate and ionomycin. The RBC bioactivities preserve the antioxidant status and are capable of rescuing activated T cells from cell death induced by serum deprivation. They are not mediated by glycosylphosphatidylinositol-linked receptors or sialic acids, and kinetic studies revealed that they hasten the entrance into the cell cycle. By using cyclosporine A (CsA) and rapamycin (Rapa) we show that the RBC bioactivities are calcineurin-dependent. Thus, treatment of T cells with CsA, but not Rapa, impaired RBC bioactivities, and preincubation of RBC with CsA completely abolished their bioactivities. We have demonstrated that RBC carry out bioactivities that are sensitive to CsA.
authors.affiliation: Lymphocyte Biology Group, IBMC, Instituto de Biologia Celular e Molecular, Porto, Portugal.
authors.forename: Ricardo F
authors.initials: RF
authors.lastname: Antunes
authors.forename: Cláudia
authors.initials: C
authors.lastname: Brandão
authors.forename: Gonçalo
authors.initials: G
authors.lastname: Carvalho
authors.forename: Cristina
authors.initials: C
authors.lastname: Girão
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Arosa
mesh_terms: D017209:Apoptosis; D019703:Calcineurin / Q000378:metabolism / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D049108:Cell Enlargement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology*; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation; D009025:Morpholines / Q000494:pharmacology; D019158:N-Acetylneuraminic Acid / Q000378:metabolism / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology; D020123:Sirolimus / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; D017261:Glycosylphosphatidylinositols; D007166:Immunosuppressive Agents; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011956:Receptors, Cell Surface; D013438:Sulfhydryl Compounds; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D016572:Cyclosporine; D019703:Calcineurin; D019158:N-Acetylneuraminic Acid; D020123:Sirolimus