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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 (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 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. Social Bookmarking                   What's this? Submitted November 6, 2002 Accepted January 6, 2003 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, Bart Barlogie, and Qing Yi* Myeloma Institute for Research and Therapy and Arkansas Cancer Research Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA * Corresponding author; email: YIQing{at}uams.edu. Two common features in human immunodeficiency virus infection and acquired immune deficiency syndrome, rheumatoid arthritis and hematological 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). Addition of 2M (> 10 µg/ml) to the cultures reduced cell yield, inhibited the upregulation of surface expression of human histocompatibility leukocyte antigens (HLA)-ABC, CD1a and CD80, diminished their ability to activate T cells and compromized the generation of the type-1 T-cell response induced in allogeneic mixed lymphocyte reaction. Compared with control MoDCs, 2M-treated cells produced more interleukin (IL)-6, IL-8, and IL-10. 2M-treated cells expressed significantly fewer surface CD83, HLA-ABC and the costimulatory and adhesion molecules, and were less potent at stimulating allospecific T cells after additional 48-hour culture in the presence of tumor necrosis factor- and IL-1. During cell culture, 2M downregulated the expression of phosphorylated mitogen-activated protein (MAP) kinases ERK and 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 downregulation of the major histocompatibility complex class-I molecules, inactivation of Raf/MEK/ERK cascade and NF-B, and activation of STAT3, and merits further study to elucidate the underlying mechanisms. 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]

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