Inactivation of human white blood cells in platelet products after pathogen reduction technology treatment in comparison to gamma irradiation

Abstract

During the transfusion of blood products, the transfer of allogeneic donor white blood cells (WBCs) can mediate adverse reactions in recipients. To minimize reactions, blood components are leukoreduced and/or exposed to gamma irradiation. Nucleic acid-targeted pathogen reduction technologies (PRTs) processes are well suited for WBC inactivation. The Mirasol PRT system (CaridianBCT Biotechnologies) uses riboflavin and ultraviolet light to reduce the active pathogen load and inactivate residual WBCs in blood products used for transfusion. The aim of this study was to compare the effect of PRT treatment to gamma irradiation. WBCs were resuspended in 100% plasma or in plasma containing 65% platelet additive solution (SSP+). A single product was split into three aliquots: control, PRT treatment, or gamma irradiation. After treatment, peripheral blood mononuclear cells were isolated from products, and cell viability and functionality were assessed in limiting dilution assays (LDAs), by CD69 expression, by proliferation, and by cytokine accumulation after lipopolysaccharide addition. PRT treatment and gamma irradiation reduced the ability of the T cells to proliferate by similar degrees as evidenced by a 6 log or greater reduction in the LDA and a lack of response to several stimuli. However, gamma-irradiated T cells were still capable of up regulating surface CD69, inducing a proliferative response in allogeneic responder cells, and producing levels of proinflammatory cytokines similar to those of untreated control cells, responses that PRT-treated T cells were incapable of mediating. These in vitro results demonstrate that PRT treatment is more effective than gamma irradiation at abrogating selected WBC immune functions.