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To whom all correspondence should be addressed Please address correspondence to: James Zimring, MD PhD, Emory University School of Medicine, Woodruff Memorial Building Suite 7107A, 101 Woodruff Circle, Atlanta, GA 30322, USA (Telephone 404-712-2174, Fax 404-727-5764), jzimrin@emory.edu

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Research Funding:

Grant Support: NIH grants R01HL105613 and R01HL092977 to J.C.Z. These studies were funded in part by grants R01HL092977 and R01HL105613

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

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Journal Title:

Transfusion

Volume:

Volume 52, Number 4

Publisher:

, Pages 849-859

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2011 American Association of Blood Banks

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