Functional inactivation of white blood cells by Mirasol treatment

Abstract

The presence of white blood cells (WBCs) in blood products has been shown to contribute to the development of a variety of immune responses including both donor antirecipient and recipient antidonor responses. Mirasol PRT treatment is a pathogen reduction protocol that is based on the inactivation of nucleic acid replication after exposure to riboflavin and light and was tested for its ability to inactivate nucleated WBC function. Sets of paired WBCs from different donors who either had received Mirasol treatment or were untreated were tested for their ability to be activated in response to phorbol myristic acetate (PMA); to proliferate in response to stimuli including phytohemagglutinin PHA, anti-CD3+ anti-CD28, or allogeneic stimulator cells; to stimulate proliferation by allogeneic responder cells; and to produce cytokines in response to lipopolysaccharide (LPS) and anti-CD3+ anti-CD28. Although Mirasol PRT treatment did not significantly change the distribution of human lymphocyte subpopulations, there were significant functional changes. Mirasol PRT treatment inhibited activation in response to PMA and completely inhibited proliferation in response to PHA, anti-CD3+ anti-CD28, or allogeneic stimulator cells. Mirasol PRT treatment also prevented the cells' ability to act as antigen-presenting cells and the ability to produce cytokines in response to stimuli such as LPS or anti-CD3+ anti-CD28. Mirasol PRT treatment is able to functionally inactivate WBCs in blood products along with inactivating pathogens and should prevent immunological consequences resulting from the presence of WBCs in blood products.