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Prepublished online as a Blood First Edition Paper on January 16, 2003; DOI 10.1182/blood-2002-11-3368. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-11-3368v1 101/10/4005    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 Xie, J. Articles by Yi, Q. Search for Related Content PubMed PubMed Citation Articles by Xie, J. Articles by Yi, Q. Related Collections Immunobiology Neoplasia Cell Adhesion and Motility Signal Transduction Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 May 2003, Vol. 101, No. 10, pp. 4005-4012 IMMUNOBIOLOGY 2-Microglobulin as a negative regulator of the immune system: high concentrations of the protein inhibit in vitro generation of functional dendritic cells Jin Xie, Ying Wang, Muta E. Freeman III, Bart Barlogie, and Qing Yi From the Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock. Two common features in human immunodeficiency virus infection and acquired immunodeficiency syndrome, rheumatoid arthritis, and hematologic malignancies including multiple myeloma are elevated serum levels of 2-microglobulin (2M) and activation or inhibition of the immune system. We hypothesized that 2M at high concentrations may have a negative impact on the immune system. In this study, we examined the effects of 2M on monocyte-derived dendritic cells (MoDCs). The addition of 2M (more than 10 µg/mL) to the cultures reduced cell yield, inhibited the up-regulation of surface expression of human histocompatibility leukocyte antigen (HLA)-ABC, CD1a, and CD80, diminished their ability to activate T cells, and compromised generation of the type-1 T-cell response induced in allogeneic mixed-lymphocyte reaction. Compared with control MoDCs, 2M-treated cells produced more interleukin-6 (IL-6), IL-8, and IL-10. 2M-treated cells expressed significantly fewer surface CD83, HLA-ABC, costimulatory molecules, and adhesion molecules and were less potent at stimulating allospecific T cells after an additional 48-hour culture in the presence of tumor necrosis factor- and IL-1. During cell culture, 2M down-regulated the expression of phosphorylated mitogen-activated protein (MAP) kinases, extracellular signal-related kinase (ERK), and mitogen-induced extracellular kinase (MEK), inhibited nuclear factor-B (NF-B), and activated signal transducer and activator of transcription-3 (STAT3) in treated cells, all of which are involved in cell differentiation and proliferation. Thus, our study demonstrates that 2M at high concentrations retards the generation of MoDCs, which may involve down-regulation of major histocompatibility complex class I molecules, inactivation of Raf/MEK/ERK cascade and NF-B, and activation of STAT3, and it merits further study to elucidate the underlying mechanisms. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. v. Rhee Idiotype Vaccination Strategies in Myeloma: How to Overcome a Dysfunctional Immune System Clin. Cancer Res., March 1, 2007; 13(5): 1353 - 1355. [Full Text] [PDF] S. Wang, J. Yang, J. Qian, M. Wezeman, L. W. Kwak, and Q. Yi Tumor evasion of the immune system: inhibiting p38 MAPK signaling restores the function of dendritic cells in multiple myeloma Blood, March 15, 2006; 107(6): 2432 - 2439. [Abstract] [Full Text] [PDF] R. H. Prabhala, P. Neri, J. E. Bae, P. Tassone, M. A. Shammas, C. K. Allam, J. F. Daley, D. Chauhan, E. Blanchard, H. S. Thatte, et al. Dysfunctional T regulatory cells in multiple myeloma Blood, January 1, 2006; 107(1): 301 - 304. [Abstract] [Full Text] [PDF] M. Ando, A. Shibuya, M. Yasuda, N. Azuma, K. Tsuchiya, T. Akiba, and K. Nitta Impairment of innate cellular response to in vitro stimuli in patients on continuous ambulatory peritoneal dialysis Nephrol. Dial. Transplant., November 1, 2005; 20(11): 2497 - 2503. [Abstract] [Full Text] [PDF] J-E Gottenberg, M Busson, J Cohen-Solal, F Lavie, K Abbed, R P Kimberly, J Sibilia, and X Mariette Correlation of serum B lymphocyte stimulator and {beta}2 microglobulin with autoantibody secretion and systemic involvement in primary Sjogren's syndrome Ann Rheum Dis, July 1, 2005; 64(7): 1050 - 1055. [Abstract] [Full Text] [PDF] D. E. Spaner Amplifying cancer vaccine responses by modifying pathogenic gene programs in tumor cells J. Leukoc. Biol., August 1, 2004; 76(2): 338 - 351. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020