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Blood, 15 February 2004, Vol. 103, No. 4, pp. 1438-1444. Prepublished online as a Blood First Edition Paper on October 16, 2003; DOI 10.1182/blood-2003-05-1491. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-05-1491v1 103/4/1438    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 Holling, T. M. Articles by van den Elsen, P. J. Search for Related Content PubMed PubMed Citation Articles by Holling, T. M. Articles by van den Elsen, P. J. Related Collections Immunobiology Neoplasia Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Regulation of MHC class II expression in human T-cell malignancies Tjadine M. Holling, Erik Schooten, Anton W. Langerak, and Peter J. van den Elsen From the Division of Molecular Biology, Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands; Department of Immunology, Erasmus Medical Center, University Medical Center Rotterdam, the Netherlands. Expression of major histocompatibility complex (MHC) class II molecules in human activated T cells is under normal circumstances regulated exclusively by the CIITA-PIII subtype of the class II transactivator (CIITA). In this study, we show that the absence of MHC class II expression in leukemic T cells was due to a lack of expression of CIITA, whereas in T-lymphoma cells, expression of CIITA correlated with expression of MHC class II. Interestingly, activation of a CIITA-promoter (P)III–reporter construct was not affected in leukemic T cells. This revealed that the absence of endogenous CIITA expression was not caused by a lack of transcription factors critical for CIITA-PIII activation but suggests the involvement of an epigenetic silencing mechanism. Subsequent analysis showed that the lack of human leukocyte antigen–DR (HLA-DR) expression correlated with hypermethylation of CIITA-PIII in leukemic T-cell lines and in primary T-cell acute lymphoblastic leukemia (T-ALL) and a T-cell prolymphocytic leukemia (T-PLL). Treatment of leukemic T-cell lines with a demethylation agent showed re-expression of CIITA-PIII and HLA-DRA. Furthermore, in vitro methylation of CIITA-PIII and subsequent assessment of CIITA-PIII activity in Jurkat leukemic T cells resulted in reduction of constitutive and CREB-1 (cyclic adenosine monophosphate [cAMP]–response element binding protein 1)–induced promoter activity. Together, these results argue for an important role of DNA hyper-methylation in the control of CIITA expression in leukemic T cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. M. Holling, M. W. T. Bergevoet, L. Wilson, M. C. J. A. Van Eggermond, E. Schooten, R. D. M. Steenbergen, P. J. F. Snijders, M. J. Jager, and P. J. Van den Elsen A Role for EZH2 in Silencing of IFN-{gamma} Inducible MHC2TA Transcription in Uveal Melanoma J. Immunol., October 15, 2007; 179(8): 5317 - 5325. [Abstract] [Full Text] [PDF] H.-R. Kim, K.-A Hwang, K.-C. Kim, and I. Kang Down-Regulation of IL-7R{alpha} Expression in Human T Cells via DNA Methylation J. Immunol., May 1, 2007; 178(9): 5473 - 5479. [Abstract] [Full Text] [PDF] L. M. Rimsza, R. A. Roberts, E. Campo, T. M. Grogan, S. Bea, I. Salaverria, A. Zettl, A. Rosenwald, G. Ott, H. K. Muller-Hermelink, et al. Loss of major histocompatibility class II expression in non-immune-privileged site diffuse large B-cell lymphoma is highly coordinated and not due to chromosomal deletions Blood, February 1, 2006; 107(3): 1101 - 1107. [Abstract] [Full Text] [PDF] A. H. Undale, P. J. van den Elsen, and E. Celis Antigen-independent acquisition of MHC class II molecules by human T lymphocytes Int. Immunol., October 1, 2004; 16(10): 1523 - 1533. [Abstract] [Full Text] [PDF]

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