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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 (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 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 Social Bookmarking                   What's this? Submitted October 17, 2003 Accepted November 22, 2003 IgG anti-platelet 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* Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada; Canadian Blood Services, Toronto, ON, Canada Department of Medicine, University of Toronto, Toronto, ON, Canada Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada * Corresponding author; email: semplej{at}smh.toronto.on.ca. The mechanisms responsible for 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<0.001) enhanced antibody production. Isotype analysis revealed that CD8+ T cells suppressed 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 negative lymphocytes within 24 hours after the first transfusion. The early IFN- response correlated with nitric oxide-dependent splenic cytotoxicity (p<0.001). In asialo GM1-depleted mice transfused with allogeneic platelets, the IFN- production, splenic cytotoxicity and IgG anti-donor antibody response were significantly suppressed. These results demonstrate that IgG anti-platelet 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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