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Blood, 1 April 2004, Vol. 103, No. 7, pp. 2705-2709. Prepublished online as a Blood First Edition Paper on December 4, 2003; DOI 10.1182/blood-2003-10-3552. This Article Full Text Full Text (PDF) Erratum (v103,p3643) All Versions of this Article: 2003-10-3552v1 103/7/2705    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sayeh, E. Articles by Semple, J. W. Search for Related Content PubMed PubMed Citation Articles by Sayeh, E. Articles by Semple, J. W. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Transfusion Medicine Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY IgG antiplatelet immunity is dependent on an early innate natural killer cell–derived interferon- response that is regulated by CD8+ T cells Ebrahim Sayeh, Katherine Sterling, Edwin Speck, John Freedman, and John W. Semple From the Department of Laboratory Medicine and Pathobiology, St Michael's Hospital, Departments of Pharmacology, Medicine and Laboratory Medicine and Pathobiology, University of Toronto, Canadian Blood Services and the Toronto Platelet Immunobiology Group, Toronto, ON, Canada. The mechanisms responsible for immunoglobulin G (IgG) immunity against allogeneic platelets are poorly understood. We studied the role that murine recipient CD8+ T and natural killer (NK) cells play in immunity against allogeneic platelets. BALB/c mice were depleted of the cells by cell-specific antibodies, transfused weekly with platelets from C57BL/6 mice, and serum IgG antidonor antibodies were measured by flow cytometry. While allogeneic platelet transfusions into wild-type recipients stimulated IgG antidonor antibodies in all mice by the fifth transfusion, CD8-depleted mice had significantly (P < .001) enhanced antibody production. Isotype analysis revealed that CD8+ T cells suppressed T-helper 2 (Th2)-associated IgG1 but enhanced Th1-associated IgG2a. Compared with wild-type mice, platelet transfusions into CD8-depleted mice stimulated enhanced intracellular interferon (IFN)- production by CD4- lymphocytes within 24 hours after the first transfusion. The early IFN- response correlated with nitric oxide-dependent splenic cytotoxicity (P < .001). In asialo ganglioside monosialic acid 1 (GM1)-depleted mice transfused with allogeneic platelets, the IFN- production, splenic cytotoxicity, and IgG antidonor antibody response were significantly suppressed. These results demonstrate that IgG antiplatelet immunity is dependent on an early NK cell-derived IFN- response that is negatively regulated by CD8+ T cells and suggest that targeting innate NK cell responses may significantly reduce platelet alloimmunization. (Blood. 2004;103:2705-2709) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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