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Blood, 1 May 2004, Vol. 103, No. 9, pp. 3431-3439. Prepublished online as a Blood First Edition Paper on January 15, 2004; DOI 10.1182/blood-2003-02-0400. This Article Full Text (PDF) All Versions of this Article: 2003-02-0400v1 103/9/3431    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Epling-Burnette, P K Articles by Loughran, T. P Search for Related Content PubMed PubMed Citation Articles by Epling-Burnette, P K Articles by Loughran, T. P Social Bookmarking                   What's this? Submitted February 10, 2003 Accepted December 10, 2003 Dysregulated NK Receptor Expression in Patients with Lymphoproliferative Disease of Granular Lymphocytes P K Epling-Burnette*, Jeffrey S Painter, Pratima Chaurasia, Fanqi Bai, Sheng Wei, Julie Y Djeu, and Thomas P Loughran Hematolotic Malignancies, H. Lee Moffitt Cancer Center, Tampa, FL, USA; Department of Interdisciplinary Oncology, University of South Florida, Tampa, FL, USA; Research, Veterans' Administration Hospital, Tampa, FL, USA Hematolotic Malignancies, H. Lee Moffitt Cancer Center, Tampa, FL, USA; Department of Interdisciplinary Oncology, University of South Florida, Tampa, FL, USA Immunology Program, H. Lee Moffitt Cancer Center, Tampa, FL, USA; Department of Interdisciplinary Oncology, University of South Florida, Tampa, FL, USA Center Director, Penn State Cancer Center, Hershey, PA, USA * Corresponding author; email: burnetpk{at}moffitt.usf.edu. The NK type of Lymphoproliferative Disease of Granular Lymphocytes (LDGL) is associated with the expansion of CD3-, CD16+ and/or CD56+ lymphocytes. We have examined the repertoire of NK receptors expressed on these cells and delineated the functional activity. We found skewed NK receptor expression on patient NK cells. Reactivity to a single anti-KIR antibody was noted in 7 of 13 patients. LDGL patients variably expressed NKp30, NKp44, and NKp46 RNA. In contrast, CD94 and its inhibitory heterodimerization partner NKG2A were homogenously expressed at high levels on these NK cells. Interestingly, these patients expressed a large number of activating KIR receptors by genotype analysis. Semi-quantitative RT-PCR demonstrated that lower than normal levels of RNA of the inhibitory KIR was present in some patients in contrast to normal NK cells. Consistent with a high level of activating receptors, we found the NK-LDGL cells have potent cytolytic function in both direct and redirected cytotoxicity assays. These results demonstrate that patients with NK-LDGL have an increased activating to inhibitory KIR ratio. This altered ratio might induce inappropriate lysis or cytokine production and impact the disease pathogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Zambello and G. Semenzato Large granular lymphocyte disorders: new etiopathogenetic clues as a rationale for innovative therapeutic approaches Haematologica, October 1, 2009; 94(10): 1341 - 1345. [Full Text] [PDF] P. K. Epling-Burnette, L. Sokol, X. Chen, F. Bai, J. Zhou, M. A. Blaskovich, J. Zou, J. S. Painter, T. D. Edwards, L. Moscinski, et al. 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Blood (ASH Annual Meeting Abstracts), November 16, 2005; 106(11): 2404 - 2404. [Abstract] A. P. Williams, A. R. Bateman, and S. I. Khakoo HANGING IN THE BALANCE: KIR and Their Role in Disease Mol. Interv., August 1, 2005; 5(4): 226 - 240. [Abstract] [Full Text] [PDF] P.K. Epling-Burnette, F. Bai, J. S. Painter, S. Wei, J. Y. Djeu, and T. P. Loughran Reduced Inhibitory KIR Receptors in Patients with NK-Lymphoproliferative Disease of Large Granular Lymphocytes (NK-LDGL) Leads to Dysregulated Killing. Blood (ASH Annual Meeting Abstracts), November 16, 2004; 104(11): 2661 - 2661. [Abstract]

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