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Blood, 16 April 2009, Vol. 113, No. 16, pp. 3875-3884. Prepublished online as a Blood First Edition Paper on January 28, 2009; DOI 10.1182/blood-2008-09-177055. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-09-177055v1 113/16/3875    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yu, J. Articles by Hsu, K. C. Search for Related Content PubMed PubMed Citation Articles by Yu, J. Articles by Hsu, K. C. Related Collections Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Breaking tolerance to self, circulating natural killer cells expressing inhibitory KIR for non-self HLA exhibit effector function after T cell–depleted allogeneic hematopoietic cell transplantation Junli Yu1, Jeffrey M. Venstrom2, Xiao-Rong Liu1, James Pring1, Reenat S. Hasan1, Richard J. O'Reilly3, and Katharine C. Hsu2 1 Immunology Program, Sloan-Kettering Institute for Cancer Research, 2 Department of Medicine, and 3 Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY Alloreactive natural killer (NK) cells are an important influence on hematopoietic stem cell transplantation (HSCT) outcome. In HLA-mismatched HSCT, alloreactivity occurs when licensed donor NK cells expressing inhibitory killer Ig-like receptors (KIR) for donor MHC class I ligands recognize the lack of the class I ligands in the mismatched recipient ("missing self"). Studies in HLA-matched HSCT, however, have also demonstrated improved outcome in patients lacking class I ligands for donor inhibitory KIR ("missing ligand"), indicating that classically nonlicensed donor NK cells expressing KIR for non-self MHC class I ligands may exhibit functional competence in HSCT. We examined NK function in 16 recipients of T cell–depleted allografts from HLA-identical or KIR-ligand matched donors after myeloablative therapy. After HSCT, nonlicensed NK cells expressing inhibitory KIR for non-self class I exhibit robust intracellular IFN- and cytotoxic response to target cells lacking cognate ligand, gradually becoming tolerized to self by day 100. These findings could not be correlated with cytokine environment or phenotypic markers of NK development, nor could they be attributed to non-KIR receptors such as CD94/NKG2A. These findings confirm that NK alloreactivity can occur in HLA-matched HSCT, where tolerance to self is either acquired by the stem cell–derived NK cell after exiting the bone marrow or where tolerance to self can be temporarily overcome. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. M. Venstrom, J. Zheng, N. Noor, K. E. Danis, A. W. Yeh, I. Y. Cheung, B. Dupont, R. J. O'Reilly, N.-K. V. Cheung, and K. C. Hsu KIR and HLA Genotypes Are Associated with Disease Progression and Survival following Autologous Hematopoietic Stem Cell Transplantation for High-Risk Neuroblastoma Clin. Cancer Res., December 1, 2009; 15(23): 7330 - 7334. [Abstract] [Full Text] [PDF] S. Cooley and J. S. Miller "Self"-reflection by KIR Blood, July 2, 2009; 114(1): 2 - 3. [Abstract] [Full Text] [PDF]

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