| Background:Transfusion-associated graft-versus-host disease (TA-GVHD) is an immunological attack of the host cells and tissues after transfusion, primarily caused by viable T lymphocvtes contained in the donor blood which have not been recognized as foreign and rejected by the host's lymphocytes, and which survive and proliferate in the host.TA-GVHD is particularly likely to occur in those with certain forms of immunodeficiency and who undergo transfusions from donors who share HLA haplotype with the recipient. TA-GVHD is an immune reaction mediated by T lymphocytes. Itspathogenesis is dependent on three factors: 1) the unmunopotency of the recipient; 2) the HLA histocompatibility between the donor and the recipient, and 3) the immunocompetence of the T lymphocytes contained in the donor blood The incidence and the seriousness have close relation to the amount of transfused T lymphocytes. The more T lymphocytes transfused, the higher the incidence of TA-GVHD, and the higher the mortality it induces. The average lymphocyte concentration is more than 2><109/L in whole blood, red cells and platelet concentrate prepared for clinical transfusions in our country, which will induce TA-GVHD.Concern about TA-GVHD associated with serious morbidity and mortality in 80 to 90 percent of affected patients and in the absence of effective treatment, attention is focused on potential preventive measures. Methods currently used for prevention of TA-GVHD include: gamma radiation, white blood cell filtration, and photochemical treatment with psoralen plus ultraviolet A light. The white cell filtration which was used primarily in reducing the risk of cytomegalovirus infection and allo-immunization, was found to be a new way of preventing TA-GVHD, although ineffectiveness of filtration has also been reported in a patient with Hodgkin's disease who had received filtered red cell units. Lymphocytes are sensitive to gamma irradiation and lose their ability to proliferate and differentiate due to DNA damage after irradiation. Therefore, the irradiated cells are not capable to attack the host or to be rejected by host, and can eventually survive in the host. The appropriate amount of gamma radiation necessary to not only inhibit T lymphocyte function, but also maintain the function and viability of other cellular elements to be determined. A recent survey conducted by AABB (American Associationof Blood Banks) found that the radiation doses ranging from 15Gy to 50Gy are used in different countries.In this study, we determined the optimal dosage of gamma radiation by investigating the transformation of T lymphocytes, activation, proliferation, cytokine generation, and the apoptosis of red cells and platelets under different doses of radiation. We also observed a variety of T lymphocyte subsets after white cell filtration and gamma irradiation.Methods:Units of whole blood with heparin for anti-agglutination were collected from healthy random-donors from The Blood Bank of Zhejiang Province. They were initially divided into three groups: control group, irradiation group, and filtration group. The irradiated group was treated with gamma radiation at dose of 20Gy, 25Gy and 30Gy. The changes of CD3 ,CD4~, and CDS" T cells and the apoptosis of red cells and platelets were measured by flow cytometry . The mononuclear cells isolated from each of the groups were incubated with phytohemagglutinin (PHA) and lipopolysacchande (LPS) in vitro. The status of the lymphocyte activation-induced antigens CD69, CD25, HLA-DR were determined by flow cytometry. The supematants from each sample after 24 hours and 72 hours in vitro culture were analyzed by enzyme-linked immunoadsorbent assay (ELISA) for quantities of IL-2, TNF,, IFN- Y T lymphocyte proliferation was determined by MIT assay.Results:Lymphocytes in the filtration group were significantly reduced compared to the control group (PO.01) .The percentage of CD3~,CD4\CD8~ cells were decreased with increasing doses of gamma radiation, which were significantly different...
|
PDF Full Text Request