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Blood, 15 February 2005, Vol. 105, No. 4, pp. 1558-1565. Prepublished online as a Blood First Edition Paper on October 21, 2004; DOI 10.1182/blood-2003-07-2476. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-07-2476v1 105/4/1558    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 Dierksheide, J. E. Articles by VanBuskirk, A. M. Search for Related Content PubMed PubMed Citation Articles by Dierksheide, J. E. Articles by VanBuskirk, A. M. Related Collections Immunobiology Neoplasia Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY IFN- gene polymorphisms associate with development of EBV+ lymphoproliferative disease in hu PBL-SCID mice Julie E. Dierksheide, Robert A. Baiocchi, Amy K. Ferketich, Sameek Roychowdhury, Ronald P. Pelletier, Charles F. Eisenbeis, Michael A. Caligiuri, and Anne M. VanBuskirk From the Division of Surgical Oncology, Department of Surgery; Division of Hematology and Oncology, Department of Internal Medicine; Ohio State University Comprehensive Cancer Center; Division of Epidemiology and Biometrics, Department of Medical Microbiology, Virology, Immunology, and Medical Genetics; and Division of Transplantation, Department of Surgery, Ohio State University, Columbus, OH. Posttransplantation lymphoproliferative disorder (PTLD) is a devastating post-transplantation complication often associated with Epstein-Barr virus (EBV). Although the type and length of immunosuppression are risk factors, a patient's inherent immune capacity also likely contributes to this disorder. This report uses severe-combined immunodeficient mice given injections of human peripheral blood leukocytes (hu PBL-SCID [Severe Combined Immunodeficient] mice) to test the hypothesis that cytokine genotype associates with the development of EBV-associated lymphoproliferative disease (LPD). We observed that the A/A (adenosine/adenosine) genotype for base + 874 of the interferon (IFN-) gene was significantly more prevalent in PBLs producing rapid, high-penetrance LPD in hu PBL-SCID mice, compared to PBLs producing late, lowpenetrance LPD or no LPD. In examining the relationship between genotype and cytolytic T-lymphocyte (CTL) function, transforming growth factor (TGF-) inhibited restimulation of CTLs in PBLs with adenosine at IFNG base + 874, but not in PBLs homozygous for thymidine. Importantly, neutralization of TGF- in hu PBL-SCID mice injected with A/A genotype PBLs resulted in reduced LPD development and expanded human CD8+ cells. Thus, our data show that TGF- may promote tumor development by inhibiting CTL restimulation and expansion. Further, our data indicate that IFNG genotype may provide valuable information for both identifying transplant recipients at greater risk for PTLD and developing preventive and curative strategies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: Interferon (IFN-) polymorphism in posttransplantation lymphoproliferative disease Ranjit V. Thomas, Karen McAulay, Craig Higgins, Gwen Wilkie, Dorothy H. Crawford, Anne VanBuskirk, Robert Baiocchi, Amy Ferketich, Thomas Gross, Pierluigi Porcu, and Michael Caligiuri Blood 2005 106: 1502-1503. [Full Text] [PDF] This article has been cited by other articles: K. Hatta, A. Morimoto, E. Ishii, H. Kimura, I. Ueda, S. Hibi, S. Todo, T. Sugimoto, and S. Imashuku Association of transforming growth factor-{beta}1 gene polymorphism in the development of Epstein-Barr virus-related hematologic diseases Haematologica, November 1, 2007; 92(11): 1470 - 1474. [Abstract] [Full Text] [PDF] Q. Xu, J. Lee, E. Jankowska-Gan, J. Schultz, D. A. Roennburg, L. D. Haynes, S. Kusaka, H. W. Sollinger, S. J. Knechtle, A. M. VanBuskirk, et al. Human CD4+CD25low Adaptive T Regulatory Cells Suppress Delayed-Type Hypersensitivity during Transplant Tolerance J. Immunol., March 15, 2007; 178(6): 3983 - 3995. [Abstract] [Full Text] [PDF] W. H. Lim, S. Kireta, G. R. Russ, and P. T. H. Coates Human plasmacytoid dendritic cells regulate immune responses to Epstein-Barr virus (EBV) infection and delay EBV-related mortality in humanized NOD-SCID mice Blood, February 1, 2007; 109(3): 1043 - 1050. [Abstract] [Full Text] [PDF] A. L. Steed, E. S. Barton, S. A. Tibbetts, D. L. Popkin, M. L. Lutzke, R. Rochford, and H. W. Virgin IV Gamma Interferon Blocks Gammaherpesvirus Reactivation from Latency J. Virol., January 1, 2006; 80(1): 192 - 200. [Abstract] [Full Text] [PDF] V. L. Tarakanova, F. Suarez, S. A. Tibbetts, M. A. Jacoby, K. E. Weck, J. L. Hess, S. H. Speck, and H. W. Virgin IV Murine Gammaherpesvirus 68 Infection Is Associated with Lymphoproliferative Disease and Lymphoma in BALB {beta}2 Microglobulin-Deficient Mice J. Virol., December 1, 2005; 79(23): 14668 - 14679. [Abstract] [Full Text] [PDF] R. V. Thomas, K. McAulay, C. Higgins, G. Wilkie, D. H. Crawford, A. VanBuskirk, R. Baiocchi, A. Ferketich, T. Gross, P. Porcu, et al. Interferon {gamma} (IFN-{gamma}) polymorphism in posttransplantation lymphoproliferative disease Blood, August 15, 2005; 106(4): 1502 - 1503. [Full Text] [PDF]

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