title: Modulation of the alloimmune response by blood transfusions.
abstract: Blood transfusions can induce both immune activation and immunosuppression. The former is expressed by the induction of HLA alloantibodies and T cell activation, while the latter is accompanied by enhanced graft survival in transfused versus non-transfused recipients. The immunological mechanism leading to downregulation of the alloimmune response has not yet been elucidated. Possible explanations include the induction of a Th2 response by non-professional antigen presentation by the transfused blood cells and blockage of alloreactive T cell reactivity by soluble HLA and soluble FasL in the supernatant of blood components. These mechanisms, however, do not explain the observations which have shown that the degree of HLA compatibility between the transfusion donor and patient is a determining factor. Transfusions in which the donor blood shares at least one HLA-DR antigen with the recipient induce tolerance, while fully HLA-DR mismatched transfusions lead to immunization. The importance of HLA-DR sharing suggests a central role for CD4+ regulatory T cells. In this case, indirect recognition of an allopeptide in the context of self-HLA-DR on the transfusion donor by CD4+ T cells of the recipient might be the clue to the induction of tolerance. Recent data from our laboratory in fact show that CD4+ T cells specific for an allopeptide in the context of self HLA-DR are able to downregulate the alloimmune response of autologous T cells. As these regulatory T cells produce IL-10, they may also be involved in the extension of tolerance via their modulatory effect on dendritic cells. It remains to be established whether these regulatory T cells are indeed responsible for the 'blood transfusion effect' in organ transplantation.
authors.affiliation: Leiden University Medical Center, Dept. of Immunohaematology and Blood Transfusion, The Netherlands. frans.claas@wxs.nl
authors.forename: F H
authors.initials: FH
authors.lastname: Claas
authors.forename: D L
authors.initials: DL
authors.lastname: Roelen
authors.forename: J J
authors.initials: JJ
authors.lastname: van Rood
authors.forename: A
authors.initials: A
authors.lastname: Brand
mesh_terms: D001803:Blood Transfusion; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004198:Disease Susceptibility; D006680:HLA Antigens / Q000276:immunology; D006648:Histocompatibility; D006801:Humans; D007108:Immune Tolerance; D007114:Immunization; D007165:Immunosuppression Therapy; D007239:Infections / Q000209:etiology; D007518:Isoantibodies / Q000096:biosynthesis; D008213:Lymphocyte Activation; D009364:Neoplasm Recurrence, Local / Q000209:etiology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D065227:Transfusion Reaction; D014181:Transplantation Immunology
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies