| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
* Internal Medicine and
Pediatrics, University of Cincinnati College of Medicine and Veterans Affairs Medical Center, Cincinnati, OH 45220;
Division of Rheumatology, University of California, Los Angeles, School of Medicine, Los Angeles, CA 90095;
La Jolla Institute of Allergy and Immunology, San Diego, CA 92121; and
¶ University of Tennessee, Memphis, TN 38163
Many individuals develop a single or a few brief episodes of
autoimmunity from which they recover. Mechanisms that quell pathologic
autoimmunity following such a breakdown of self-tolerance are not
clearly understood. In this study, we show that in nonautoimmune mice,
dsDNA-specific autoreactive B cells exist but remain inactive. This
state of inactivation in dsDNA-specific B cells could be disrupted by
autoreactive Th cells; in this case T cells that react with peptides
from the VH region of anti-DNA Abs (hereafter called
anti-VH T cells). Immunization with anti-DNA mAb,
its 
-chain or peptides derived from its VH region
induced anti-VH Th cells, IgG anti-dsDNA Ab, and
proteinuria. The breakdown of B cell tolerance in nonautoimmune mice,
however, was short-lived: anti-DNA Ab and nephritis subsided
despite subsequent immunizations. The recovery from autoimmunity
temporally correlated with the appearance of T cells that inhibited
anti-DNA Ab production. Such inhibitory T cells secreted TGF
;
the inhibition of anti-DNA Ab production by these cells was partly
abolished by anti-TGF Ab. Even without immunization,
nonautoimmune mice possess T cells that can inhibit autoantibody
production. Thus, inhibitory T cells in nonautoimmune mice may normally
inhibit T-dependent activation of autoreactive B cells and/or reverse
such activation following stimulation by Th cells. The induction of
such inhibitory T cells may play a role in protecting nonautoimmune
mice from developing chronic autoimmunity.
This article has been cited by other articles:
|
|
 |
|
  A Guth, T Detanico, D Smith, K. Tung, C Bonorino, and L. Wysocki Spontaneous autoimmunity in mice that carry an IghV partial transgene: a required arginine in VHCDR3 Lupus, April 1, 2009; 18(4): 299 - 308. [Abstract] [PDF]
|
|
|
|
 |
|
 R. P. Singh, A. La Cava, and B. H. Hahn pConsensus Peptide Induces Tolerogenic CD8+ T Cells in Lupus-Prone (NZB x NZW)F1 Mice by Differentially Regulating Foxp3 and PD1 Molecules J. Immunol., February 15, 2008; 180(4): 2069 - 2080. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Saxena, D. W. Lienesch, M. Zhou, R. Bommireddy, M. Azhar, T. Doetschman, and R. R. Singh Dual Roles of Immunoregulatory Cytokine TGF-{beta} in the Pathogenesis of Autoimmunity-Mediated Organ Damage J. Immunol., February 1, 2008; 180(3): 1903 - 1912. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-K. Kang, M. Liu, and S. K. Datta Low-Dose Peptide Tolerance Therapy of Lupus Generates Plasmacytoid Dendritic Cells That Cause Expansion of Autoantigen-Specific Regulatory T Cells and Contraction of Inflammatory Th17 Cells J. Immunol., June 15, 2007; 178(12): 7849 - 7858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. S. Deshmukh, H. Bagavant, D. Sim, V. Pidiyar, and S. M. Fu A SmD Peptide Induces Better Antibody Responses to Other Proteins within the Small Nuclear Ribonucleoprotein Complex than to SmD Protein via Intermolecular Epitope Spreading J. Immunol., February 15, 2007; 178(4): 2565 - 2571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. H. Hahn, R. P. Singh, A. La Cava, and F. M. Ebling Tolerogenic Treatment of Lupus Mice with Consensus Peptide Induces Foxp3-Expressing, Apoptosis-Resistant, TGF{beta}-Secreting CD8+ T Cell Suppressors J. Immunol., December 1, 2005; 175(11): 7728 - 7737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Guo, D. Smith, A. Guth, K. Aviszus, and L. J. Wysocki T Cell Tolerance to Germline-Encoded Antibody Sequences in a Lupus-Prone Mouse J. Immunol., August 15, 2005; 175(4): 2184 - 2190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E N Voynova, A I Tchorbanov, T A Todorov, and T L Vassilev Breaking of tolerance to native DNA in nonautoimmune mice by immunization with natural protein/DNA complexes Lupus, July 1, 2005; 14(7): 543 - 550. [Abstract] [PDF]
|
|
|
|
|
|
H.-K. Kang, M. A. Michaels, B. R. Berner, and S. K. Datta Very Low-Dose Tolerance with Nucleosomal Peptides Controls Lupus and Induces Potent Regulatory T Cell Subsets J. Immunol., March 15, 2005; 174(6): 3247 - 3255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Tao, L. Shangwu, W. Qun, L. Yan, J. Wei, L. Junyan, G. Feili, J. Boquan, and T. Jinquan CD226 Expression Deficiency Causes High Sensitivity to Apoptosis in NK T Cells from Patients with Systemic Lupus Erythematosus J. Immunol., February 1, 2005; 174(3): 1281 - 1290. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Snyder, K. Aviszus, R. A. Heiser, D. R. Tonkin, A. M. Guth, and L. J. Wysocki Activation and Tolerance in CD4+ T Cells Reactive to an Immunoglobulin Variable Region J. Exp. Med., November 8, 2004; (2004) jem.20031234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Riemekasten, D. Langnickel, P. Enghard, R. Undeutsch, J. Humrich, F. M. Ebling, B. Hocher, T. Humaljoki, H. Neumayer, G.-R. Burmester, et al. Intravenous Injection of a D1 Protein of the Smith Proteins Postpones Murine Lupus and Induces Type 1 Regulatory T Cells J. Immunol., November 1, 2004; 173(9): 5835 - 5842. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Munthe, A. Os, M. Zangani, and B. Bogen MHC-Restricted Ig V Region-Driven T-B Lymphocyte Collaboration: B Cell Receptor Ligation Facilitates Switch to IgG Production J. Immunol., June 15, 2004; 172(12): 7476 - 7484. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-Q. Yang, A. K. Singh, M. T. Wilson, M. Satoh, A. K. Stanic, J.-J. Park, S. Hong, S. D. Gadola, A. Mizutani, S. R. Kakumanu, et al. Immunoregulatory Role of CD1d in the Hydrocarbon Oil-Induced Model of Lupus Nephritis J. Immunol., August 15, 2003; 171(4): 2142 - 2153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bommireddy, V. Saxena, I. Ormsby, M. Yin, G. P. Boivin, G. F. Babcock, R. R. Singh, and T. Doetschman TGF-{beta}1 Regulates Lymphocyte Homeostasis by Preventing Activation and Subsequent Apoptosis of Peripheral Lymphocytes J. Immunol., May 1, 2003; 170(9): 4612 - 4622. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L E Schiffer, N Hussain, X Wang, W Huang, J Sinha, M Ramanujam, and A Davidson Lowering anti-dsDNA antibodies--what's new? Lupus, December 1, 2002; 11(12): 885 - 894. [Abstract] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
