Poststorage leuko-depleted plasma inhibits T-cell proliferation and Th1 response in vitro: characterization of TGFbeta-1 as an important immunomodulatory component in stored blood

Poststorage, leuko-depleted blood transfusions have been associated with increased postoperative infections and improved allograft survival compared with prestorage leukocyte-depleted blood transfusion. Although the mechanism of this phenomenon remains to be fully elucidated, it is clear that the immunomodulatory effect is mediated by leukocytes/platelets or their products. The aim of this study was to investigate the in vitro effects of pre- and poststorage leuko-depleted plasma (LDP) and buffy coat LDP on T-cell proliferation and cytokine synthesis using multiparameter flow cytometry. In cell cultures exposed to prestorage LDP and buffy coat LDP there were no significant changes compared with fresh blood. In cell cultures exposed to poststorage LDP, T-cells showed reduced expression of CD69, CD25 (IL-2Ralpha), CD122 (IL-2Rbeta) and CD132 (IL-2Rtau) and production of TNF-alpha and IL-2 but there was no significant alteration for IFN-tau or IL-4. Changes in cytokine/cytokine receptor synthesis and T-cell proliferation were shown to be directly proportional to poststorage LDP concentration. Some of these changes were characteristic of TGFbeta-1. Addition of TGFbeta-1 neutralising antibody to poststorage LDP, negated the immunosuppressive effect on PHA-stimulated PBMC cultures. The decrease in T-cell proliferation and Th1 cytokines TNF-alpha and IL-2, may be one basis of altered immunoregulation resulting in increased rates of certain types of infections and increased graft tolerance reported in patients receiving poststorage LD blood transfusions. TGFbeta-1 is a major immunomodulatory component of poststorage LD blood transfusions.