A molecular mechanism of T cell downregulation by blood transfusion.

Pretransplant blood transfusions have been given to renal transplant recipients in order to improve graft survival since almost 20 years. Nevertheless, the mechanism involved in this tolerating effect of blood transfusions has not been revealed yet. Recent data, showing a need for sharing of at least one HLA-DR antigen between blood transfusion donor and recipient to obtain downregulation of the alloimmune response, are the basis of the present hypothesis. We postulate that HLA-DR-shared blood transfusions activate CD4+ T cells recognizing allogeneic peptides in the context of the shared HLA-DR molecule. These CD4+ T cells are able to downregulate the immune response of autologous activated (thus HLA-DR-positive) T cells directed against any allogeneic organ, sharing at least one allogeneic peptide with the blood transfusion donor. Essential in this hypothesis is that the T cells activated by the graft will pick up that allogeneic peptide from the transplanted organ and present it in the context of the shared HLA-DR molecule to the autologous regulatory CD4+ T cells, primed by the blood transfusion.