IMMUNOMODULATION FOLLOWING TRANSFUSION

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Complications associated with transfusion include alloimmunization to HLA proteins on leukocytes co- transfused with red cells (rbc) and platelets (pit)and a generalized immunosuppression. Although leukoreduction of blood components has been proposed to minimize allosensitization, there is inadequate data available to predict its benefit in recipients not immunosuppressed by malignancy or chemotherapy. The proposed study is a three arm randomized trial with recipients receiving standard blood products, leukoreduced blood products (LR), or leukoreduced blood products that have been gamma irradiated (LRG). The immunocompetent patients in this study are those undergoing cardiac surgery and were selected because transfusion support is well defined with exposure to 4-10 allogeneic donors. The production of anti- HLA antibody by recipients will be measured at 3 points after transfusion using flow cytometry. Studies testing the hypothesis that transfusions are immunosuppressive have measured clinical outcomes: recurrence of colon carcinoma, incidence of post-operative infection, or length of hospitalization. There is little data on transfusion's effect on recipient immunoregulatory cells. These studies will measure the impact of transfusion on two populations of recipient regulatory T cells: NKT and CD4+ Treg. Flow cytometry phenotyping will be used to compare these populations before and after transfusion in each individual. Cytokine phenotype and expression of regulatory genes (FoxPS, GITR, CTLA4) will be measured using flow cytometry, ELISPOT, and Realtime PCR. The number of donors sharing HLA class II epitopes with the recipient will be identified. We will also directly compare the number of mononuclear cells producing TGF- beta in samples collected prior to and after surgery as a surrogate measure of immunosuppression. These studies will provide data on specific immunoregulatory outcomes following transfusion. The data will also provide sensitization rates to guide selection of transfusion components for immunocompetent patients.