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

Abstract

<h4>Background</h4>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.<h4>Method</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.