title: In vitro transfusion of red blood cells results in decreased cytokine production by human T cells.
abstract: BACKGROUND
  Transfusion-related immunomodulation consists of both proinflammatory and anti-inflammatory responses after transfusion of blood products. Stored red blood cells (RBCs) suppress human T-cell proliferation in vitro, but the mechanism remains unknown. We hypothesized that cytokine synthesis by T cells may be inhibited when stored RBCs are present and that suppression between fresh and stored RBCs would be different.
  
  
  METHODS
  Purified human T cells were stimulated to proliferate with anti-CD3/anti-CD28 and then exposed to stored or fresh RBCs. Cells were placed in culture for 5 days. Cell culture supernatants were analyzed for the production of typical T-cell cytokines using multianalyte ELISArray kits.
  
  
  RESULTS
  Stimulated T cells proliferated. RBC exposure markedly suppressed this proliferation. Interleukin 10, interleukin 17a, interferon γ, tumor necrosis factor α, and granulocyte macrophage colony-stimulating factor were increased in response to stimulation but depressed in the presence of stored RBCs. The use of fresh RBCs also resulted in depression of these cytokines when compared with stimulated T cells with no RBCs; however, this depression was less pronounced.
  
  
  CONCLUSIONS
  T-cell activation is associated with both proinflammatory and anti-inflammatory cytokine release, comparable with patterns seen in trauma and acute injury. All of these responses are depressed by an exposure to stored RBCs. Decreased levels of these cytokines after RBC transfusion represents a potential contributor to the immunosuppressive complications seen in trauma patients after transfusion. This provides insight for future mechanistic studies to delineate the role of RBC transfusion in transfusion-related immunomodulation.
authors: From the Section on Trauma and Acute Care Surgery (L.P., C.M., A.B.), Division of General Surgery (K.L.), Department of Microbiology, Immunology and Molecular Genetics (J.W., M.W.), and Department of Pathology (D.W.), University of Kentucky, Lexington, Kentucky.
authors: Kristin
authors: K
authors: Long
authors: Jerold
authors: J
authors: Woodward
authors: Levi
authors: L
authors: Procter
authors: Marty
authors: M
authors: Ward
authors: Cindy
authors: C
authors: Meier
authors: Dennis
authors: D
authors: Williams
authors: Andrew
authors: A
authors: Bernard
mesh_terms: D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma