| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Medicine, Division of Rheumatology, Mayo Clinic and Foundation, Rochester, MN 55905
Patients with rheumatoid arthritis have a subset of CD4+ T lymphocytes that are characterized by a defect in CD28 expression. CD4+CD28- T cells frequently undergo clonal expansion in vivo. These clonotypes include autoreactive cells and persist over many years. The clonogenic potential and longevity of these T cells could be related to an altered response to apoptosis-inducing signals. To explore this possibility, CD4+CD28- T cell lines and clones were examined for their response pattern to stimuli inducing physiologic cell death. CD4+CD28- T cells were found to be resistant to apoptosis upon withdrawal of the growth factor, IL-2. To examine whether the altered sensitivity to this apoptotic signal was correlated with the expression of proteins of the bcl-2 family, the expression of bcl-2, bcl-x, and bax proteins was determined. CD28+ and CD28-CD4+ T cells could not be distinguished by the levels of bax or bcl-xL protein; however, CD4+CD28- T cells expressed higher amounts of bcl-2 protein than did CD4+CD28+ T cells. The increased bcl-2 expression in CD4+CD28- T cells was relatively independent of signals provided by exogenous IL-2. In CD28-deficient CD4+ T cells, bcl-2 was not significantly up-regulated by the addition of exogenous IL-2 and was maintained despite IL-2 withdrawal, as opposed to CD28-expressing CD4+ T cells. We propose that CD4+CD28- T cells are characterized by a dysregulation of the survival protein, bcl-2, which may favor the clonal outgrowth of autoreactive T cells and thus contribute to the pathogenesis of rheumatoid arthritis.
This article has been cited by other articles:
|
|
 |
|
  H. Hoff, K. Knieke, Z. Cabail, H. Hirseland, G. Vratsanos, G.-R. Burmester, G. Jorch, S. G. Nadler, B. Broker, K. Hebel, et al. Surface CD152 (CTLA-4) Expression and Signaling Dictates Longevity of CD28null T Cells J. Immunol., May 1, 2009; 182(9): 5342 - 5351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Fujii, L. Shao, I. Colmegna, J. J. Goronzy, and C. M. Weyand Telomerase insufficiency in rheumatoid arthritis PNAS, March 17, 2009; 106(11): 4360 - 4365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. E. Dumitriu, E. T. Araguas, C. Baboonian, and J. C. Kaski CD4+CD28null T cells in coronary artery disease: when helpers become killers Cardiovasc Res, January 1, 2009; 81(1): 11 - 19. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Studer, M. P. George, X. Zhu, Y. Song, V. G. Valentine, M. W. Stoner, J. Sethi, C. Steele, and S. R. Duncan CD28 Down-Regulation on CD4 T Cells Is a Marker for Graft Dysfunction in Lung Transplant Recipients Am. J. Respir. Crit. Care Med., October 1, 2008; 178(7): 765 - 773. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Clemenceau, R. Vivien, M. Berthome, N. Robillard, R. Garand, G. Gallot, S. Vollant, and H. Vie Effector Memory {alpha}{beta} T Lymphocytes Can Express Fc{gamma}RIIIa and Mediate Antibody-Dependent Cellular Cytotoxicity J. Immunol., April 15, 2008; 180(8): 5327 - 5334. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Gadgil, X. Zhu, F. C. Sciurba, and S. R. Duncan Altered T-Cell Phenotypes in Chronic Obstructive Pulmonary Disease Proceedings of the ATS, August 1, 2006; 3(6): 487 - 488. [Full Text] [PDF]
|
|
|
|
 |
|
 G. Henel, K. Singh, D. Cui, S. Pryshchep, W.-W. Lee, C. M. Weyand, and J. J. Goronzy Uncoupling of T-cell effector functions by inhibitory killer immunoglobulin-like receptors Blood, June 1, 2006; 107(11): 4449 - 4457. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Longhi, M. J. Hussain, R. R. Mitry, S. K. Arora, G. Mieli-Vergani, D. Vergani, and Y. Ma Functional Study of CD4+CD25+ Regulatory T Cells in Health and Autoimmune Hepatitis J. Immunol., April 1, 2006; 176(7): 4484 - 4491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhang, A. Niessner, T. Nakajima, W. Ma-Krupa, S. L. Kopecky, R. L. Frye, J. J. Goronzy, and C. M. Weyand Interleukin 12 Induces T-Cell Recruitment Into the Atherosclerotic Plaque Circ. Res., March 3, 2006; 98(4): 524 - 531. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Baeten, S. Louis, C. Braud, C. Braudeau, C. Ballet, F. Moizant, A. Pallier, M. Giral, S. Brouard, and J.-P. Soulillou Phenotypically and Functionally Distinct CD8+ Lymphocyte Populations in Long-Term Drug-Free Tolerance and Chronic Rejection in Human Kidney Graft Recipients J. Am. Soc. Nephrol., January 1, 2006; 17(1): 294 - 304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Duftner, R. Seiler, P. Klein-Weigel, H. Gobel, C. Goldberger, C. Ihling, G. Fraedrich, and M. Schirmer High Prevalence of Circulating CD4+CD28- T-Cells in Patients With Small Abdominal Aortic Aneurysms Arterioscler Thromb Vasc Biol, July 1, 2005; 25(7): 1347 - 1352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Taneja, N. Taneja, M. Behrens, M. M. Griffiths, H. S. Luthra, and C. S. David Requirement for CD28 May Not Be Absolute for Collagen-Induced Arthritis: Study with HLA-DQ8 Transgenic Mice J. Immunol., January 15, 2005; 174(2): 1118 - 1125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Snyder, T. Nakajima, P. J. Leibson, C. M. Weyand, and J. J. Goronzy Stimulatory Killer Ig-Like Receptors Modulate T Cell Activation through DAP12-Dependent and DAP12-Independent Mechanisms J. Immunol., September 15, 2004; 173(6): 3725 - 3731. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Canton, E. M. Martinez-Caceres, C. Hernandez, C. Espejo, J. Garcia-Arumi, and R. Simo CD4-CD8 and CD28 Expression in T Cells Infiltrating the Vitreous Fluid in Patients With Proliferative Diabetic Retinopathy: A Flow Cytometric Analysis Arch Ophthalmol, May 1, 2004; 122(5): 743 - 749. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-G. Hur, Y. Yun, and J. Won Rosmarinic Acid Induces p56lck-Dependent Apoptosis in Jurkat and Peripheral T Cells via Mitochondrial Pathway Independent from Fas/Fas Ligand Interaction J. Immunol., January 1, 2004; 172(1): 79 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. Vallejo, H. Yang, P. A. Klimiuk, C. M. Weyand, and J. J. Goronzy Synoviocyte-Mediated Expansion of Inflammatory T Cells in Rheumatoid Synovitis Is Dependent on CD47-Thrombospondin 1 Interaction J. Immunol., August 15, 2003; 171(4): 1732 - 1740. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Strauss, I. Knape, I. Melzner, and K.-M. Debatin Constitutive Caspase Activation and Impaired Death-Inducing Signaling Complex Formation in CD95-Resistant, Long-Term Activated, Antigen-Specific T Cells J. Immunol., August 1, 2003; 171(3): 1172 - 1182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Rajagopalan, M. K. Smart, E. V. Marietta, and C. S. David Staphylococcal enterotoxin B-induced activation and concomitant resistance to cell death in CD28-deficient HLA-DQ8 transgenic mice Int. Immunol., July 1, 2002; 14(7): 801 - 812. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Smith and M. K. Haynes Rheumatoid Arthritis--A Molecular Understanding Ann Intern Med, June 18, 2002; 136(12): 908 - 922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Saurwein-Teissl, T. L. Lung, F. Marx, C. Gschosser, E. Asch, I. Blasko, W. Parson, G. Bock, D. Schonitzer, E. Trannoy, et al. Lack of Antibody Production Following Immunization in Old Age: Association with CD8+CD28- T Cell Clonal Expansions and an Imbalance in the Production of Th1 and Th2 Cytokines J. Immunol., June 1, 2002; 168(11): 5893 - 5899. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Snyder, L.-O. Muegge, C. Offord, W. M. O'Fallon, Z. Bajzer, C. M. Weyand, and J. J. Goronzy Formation of the Killer Ig-Like Receptor Repertoire on CD4+CD28null T Cells J. Immunol., April 15, 2002; 168(8): 3839 - 3846. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-H. Lai, L.-J. Ho, K.-C. Lu, D.-M. Chang, M.-F. Shaio, and S.-H. Han Western and Chinese Antirheumatic Drug-Induced T Cell Apoptotic DNA Damage Uses Different Caspase Cascades and Is Independent of Fas/Fas Ligand Interaction J. Immunol., June 1, 2001; 166(11): 6914 - 6924. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhang, T. Bardos, K. Mikecz, A. Finnegan, and T. T. Glant Impaired Fas Signaling Pathway Is Involved in Defective T Cell Apoptosis in Autoimmune Murine Arthritis J. Immunol., April 15, 2001; 166(8): 4981 - 4986. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. Vallejo, M. Schirmer, C. M. Weyand, and J. J. Goronzy Clonality and Longevity of CD4+CD28null T Cells Are Associated with Defects in Apoptotic Pathways J. Immunol., December 1, 2000; 165(11): 6301 - 6307. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Liuzzo, J. J. Goronzy, H. Yang, S. L. Kopecky, D. R. Holmes, R. L. Frye, and C. M. Weyand Monoclonal T-Cell Proliferation and Plaque Instability in Acute Coronary Syndromes Circulation, June 27, 2000; 101(25): 2883 - 2888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. Vallejo, L. O. Mugge, P. A. Klimiuk, C. M. Weyand, and J. J. Goronzy Central Role of Thrombospondin-1 in the Activation and Clonal Expansion of Inflammatory T Cells J. Immunol., March 15, 2000; 164(6): 2947 - 2954. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ina, J. Itoh, K. Fukushima, K. Kusugami, T. Yamaguchi, K. Kyokane, A. Imada, D. G. Binion, A. Musso, G. A. West, et al. Resistance of Crohn's Disease T Cells to Multiple Apoptotic Signals Is Associated with a Bcl-2/Bax Mucosal Imbalance J. Immunol., July 15, 1999; 163(2): 1081 - 1090. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. Vallejo, J. C. Brandes, C. M. Weyand, and J. J. Goronzy Modulation of CD28 Expression: Distinct Regulatory Pathways During Activation and Replicative Senescence J. Immunol., June 1, 1999; 162(11): 6572 - 6579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. N. Vallejo, C. M. Weyand, and J. J. Goronzy Functional Disruption of the CD28 Gene Transcriptional Initiator in Senescent T Cells J. Biol. Chem., January 19, 2001; 276(4): 2565 - 2570. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
