Blood transfusion, blood storage and immunomodulation

Allogeneic blood transfusion is the most frequent allotransplantation procedure performed on a routine basis with no prior HLA-typing. Roughly 50% of the recipients of unprocessed red cells and platelets become alloimmunized. Evidence also exists for some degree of transfusion-induced immunosuppression. Prior transfusion has been shown to enhance kidney transplant survival and evidence of an increase in tumor recurrence and of infectious complications has also been presented. The presence of donor antigen-presenting cells appears to be a prerequisite for alloimmunization and they must be both viable and capable of presenting a costimulatory signal in order to induce IL-2 secretion and proliferation of responding CD4 T cells. APCs presenting antigen but no costimulatory signal can induce non-responsiveness in CD4 T cells, a possible mechanism of transfusion-induced immunosuppression. APCs in refrigerated blood continue to present antigen but progressively lose their ability to provide costimulation. By day 14 costimulatory capacity is absent and transfusion of such blood should not alloimmunize but could induce some degree of immunosuppression. Further refrigerated storage in excess of 2 to 3 weeks leads to induction of apoptosis in contaminating leukocytes. We have found that alloantigens-expressed on such cells do not appear to be recognized by responder T cells and transfusion of blood stored in excess of 3 weeks should neither alloimmunize nor immunosuppress.