HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Caudill, C. M. Articles by Griffin, T. A. Search for Related Content PubMed PubMed Citation Articles by Caudill, C. M. Articles by Griffin, T. A.

T Cells Lacking Immunoproteasome Subunits MECL-1 and LMP7 Hyperproliferate in Response to Polyclonal Mitogens¹

Christy M. Caudill^*, Krupakar Jayarapu^*, Laura Elenich^2,, John J. Monaco, Robert A. Colbert^* and Thomas A. Griffin^3,*

^* William S. Rowe Division of Rheumatology, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH 45229; and Department of Molecular Genetics, University of Cincinnati College of Medicine, Cincinnati, OH 45267

Immunoproteasomes comprise a specialized subset of proteasomes that is defined by the presence of three catalytic immunosubunits: LMP2, MECL-1 (LMP10), and LMP7. Proteasomes in general serve many cellular functions through protein degradation, whereas the specific function of immunoproteasomes has been thought to be largely, if not exclusively, optimization of MHC class I Ag processing. In this report, we demonstrate that T cells from double knockout mice lacking two of the immunosubunits, MECL-1 and LMP7, hyperproliferate in vitro in response to various polyclonal mitogens. We observe hyperproliferation of both CD4⁺ and CD8⁺ T cell subsets and demonstrate accelerated cell cycling. We do not observe hyperproliferation of T cells lacking only one of these subunits, and thus hyperproliferation is independent of either reduced MHC class I expression in LMP7^–/– mice or reduced CD8⁺ T cell numbers in MECL-1^–/– mice. We observe both of these latter two phenotypes in MECL-1/LMP7^–/– mice, which indicates that they also are independent of each other. Finally, we provide evidence of in vivo T cell dysfunction by demonstrating increased numbers of central memory phenotype CD8⁺ T cells in MECL-1/LMP7^–/– mice. In summary, this novel phenotype of hyperproliferation of T cells lacking both MECL-1 and LMP7 implicates a specific role for immunoproteasomes in T cell proliferation that is not obviously connected to MHC class I Ag processing.

This article has been cited by other articles:

				Z. Yang, D. Gagarin, G. St. Laurent III, N. Hammell, I. Toma, C.-a. Hu, A. Iwasa, and T. A. McCaffrey Cardiovascular Inflammation and Lesion Cell Apoptosis: A Novel Connection via the Interferon-Inducible Immunoproteasome Arterioscler Thromb Vasc Biol, August 1, 2009; 29(8): 1213 - 1219. [Abstract] [Full Text] [PDF]

				D. M. W. Zaiss, N. de Graaf, and A. J. A. M. Sijts The Proteasome Immunosubunit Multicatalytic Endopeptidase Complex-Like 1 Is a T-Cell-Intrinsic Factor Influencing Homeostatic Expansion Infect. Immun., March 1, 2008; 76(3): 1207 - 1213. [Abstract] [Full Text] [PDF]

				P. Deol, D. M. W. Zaiss, J. J. Monaco, and A. J. A. M. Sijts Rates of Processing Determine the Immunogenicity of Immunoproteasome-Generated Epitopes J. Immunol., June 15, 2007; 178(12): 7557 - 7562. [Abstract] [Full Text] [PDF]

				K. C. Pang, M. T. Sanders, J. J. Monaco, P. C. Doherty, S. J. Turner, and W. Chen Immunoproteasome Subunit Deficiencies Impact Differentially on Two Immunodominant Influenza Virus-Specific CD8+ T Cell Responses J. Immunol., December 1, 2006; 177(11): 7680 - 7688. [Abstract] [Full Text] [PDF]