Alloimmunization to transfused platelets requires priming of CD4+ T cells in the splenic microenvironment in a murine model

• Authors: Christopher Raleigh Gilson, Emory University; James C Zimring, Emory University
• Journal Title: Transfusion
• Volume: Volume 52, Number 4
• Publisher: Wiley-Blackwell | 2012-04, Pages 849-859
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1111/j.1537-2995.2011.03346.x
• Subjects: Health Sciences, Medicine and Surgery; Health Sciences, General

Abstract

Background Alloantibodies are a clinically significant sequelae of platelet transfusion, potentially rendering patients refractory to ongoing platelet transfusion support. These antibodies are often IgG class switched, suggesting the involvement of CD4+ T cell help; however, platelet specific CD4+ T cells have not been visualized in vivo and specifics of their stimulation are not completely understood. Study Design and Methods A murine model of alloimmunization to transfused platelets was developed to allow in vivo assessment and characterization of CD4+ T cells specific for platelet MHC alloantigen. Platelets were harvested from BALB/c mice, filter leukoreduced, and transfused into C57BL/6 recipients. Platelet specific CD4+ T cell responses were visualized by using a TCR transgenic mouse that detects peptide from donor MHC I presented on recipient MHC II. Antibody responses were determined by indirect immunofluorescence using BALB/c donor targets. Results C57BL/6 recipients of BALB/c leukoreduced platelet transfusions produced anti-BALB/c antibodies, with proliferation of antigen specific CD4+ T cells seen in the spleen but not lymph nodes or liver. Depletion of recipient CD4+ cells or splenectomy independently abrogated the alloantibody response. Conclusion We report a novel model to study antigen-specific CD4+ T cells during alloimmunization to platelet transfusion. The presented data support a critical role for CD4+ T cell help in the humoral response to platelet transfusion and establish the spleen as a required microenvironment for effective CD4+ T cell priming against donor platelet derived MHC I.