Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 5/2003

Open Access 01-10-2003 | Research article

Prevalence, clinical relevance and characterization of circulating cytotoxic CD4+CD28- T cells in ankylosing spondylitis

Authors: Christina Duftner, Christian Goldberger, Albrecht Falkenbach, Reinhard Würzner, Barbara Falkensammer, Karl P Pfeiffer, Elisabeth Maerker-Hermann, Michael Schirmer

Published in: Arthritis Research & Therapy | Issue 5/2003

Login to get access

Abstract

Circulating CD3+CD4+CD28- cells exhibit reduced apoptosis and were found to be more enriched in patients with ankylosing spondylitis than in age-matched healthy control individuals (7.40 ± 6.6% versus 1.03 ± 1.0%; P < 0.001). Levels of CD4+CD28- T cells correlate with disease status as measured using a modified metrology score, but they are independent of age and duration of ankylosing spondylitis. CD4+CD28- T cells produce IFN-γ and perforin, and thus they must be considered proinflammatory and cytotoxic. These T cells share phenotypic and functional properties of natural killer cells, strongly expressing CD57 but lacking the lymphocyte marker CD7. MHC class I recognizing and activating natural killer cell receptors on the surface of CD4+CD28- T cells may be involved in a HLA-B27 mediated co-stimulation of these proinflammatory and cytotoxic cells.
Literature
1.
Khare SD, Luthra HS, David CS: Spontaneous inflammatory arthritis in HLA-B27 transgenic mice lacking beta 2-microglobulin: a model of human spondyloarthropathies. J Exp Med. 1995, 182: 1153-1158. 10.1084/jem.182.4.1153.CrossRefPubMed
2.
Scofield RH, Kurien B., Gross T, Warren WL, Harley JB: HLA-B27 binding of peptide from its own sequence and similar peptides from bacteria: implications for spondyloarthropathies. Lancet. 1995, 345: 1542-1544. 10.1016/S0140-6736(95)91089-1.CrossRefPubMed
3.
Hermann E, Yu DT, Meyer zum Buschenfelde KH, Fleischer B: HLA-B27-restricted CD8 T cells derived from synovial fluids of patients with reactive arthritis and ankylosing spondylitis. Lancet. 1993, 342: 646-650. 10.1016/0140-6736(93)91760-J.CrossRefPubMed
4.
Ugrinovic S, Mertz A, Wu P, Braun J, Sieper J: A single nonamer from the Yersinia 60-kDA heat shock protein is the target of HLA-B27 restricted CTL response in Yersinia-induced reactive arthritis. J Immunol. 1997, 159: 5715-5723.PubMed
5.
Schirmer M, Goldberger C, Wurzner R, Duftner C, Pfeiffer KP, Clausen J, Neumayr G, Falkenbach A: Circulating cytotoxic CD8+ CD28- T cells in ankylosing spondylitis. Arthritis Res. 2002, 4: 71-76. 10.1186/ar386.PubMedCentralCrossRefPubMed
6.
Boyle LH, Goodall JC, Opat SS, Gaston JS: The recognition of HLA-B27 by human CD4+ T lymphocytes. J Immunol. 2001, 167: 2619-2624.CrossRefPubMed
7.
Turner MJ, Colbert RA: HLA-B27 and pathogenesis of spondyloarthropathies. Curr Opin Rheumatol. 2002, 14: 367-372. 10.1097/00002281-200207000-00006.CrossRefPubMed
8.
Breban M, Hammer RE, Richardson JA, Taurog JD: Transfer of the inflammatory disease of HLA-B27 transgenic rats by bone marrow engraftment. J Exp Med. 1993, 178: 1607-1616. 10.1084/jem.178.5.1607.CrossRefPubMed
9.
Breban M, Fernandez-Sueiro JL, Richardson JA, Hadavand RR, Maika SD, Hammer RE, Taurog JD: T cells, but not thymic exposure to HLA-B27, are required for the inflammatory disease of HLA-B27 transgenic rats. J Immunol. 1996, 157: 794-803.
10.
O'Sullivan FX, Vogelweid CM, Besch-Williford CL, Walker SE: Differential effects of CD4+ T cell depletion on inflammatory central nervous system disease, arthritis and sialadenitis in MRL/lpr mice. J Autoimmun. 1995, 8: 163-175. 10.1006/jaut.1995.0013.CrossRefPubMed
11.
Khare SD, Bull MJ, Hanson J, Luthra HS, David CS: Spontaneous inflammatory disease in HLA-B27 transgenic mice is independent of MHC class II molecules: a direct role for B27 H chains and not B27-derived peptides. J Immunol. 1998, 160: 101-106.PubMed
12.
Brand JM, Neustock P, Kruse A, Alvarez-Ossorio L, Schnabel A, Kirchner H: Stimulation of whole blood cultures in patients with ankylosing spondylitis by a mitogen derived from Mycoplasma arthritidis (MAS) and other mitogens. Rheumatol Int. 1997, 16: 207-211. 10.1007/BF01330297.CrossRefPubMed
13.
Braun J, Bollow M, Neure L, Seipelt E, Seyrekbasan F, Herbst H, Eggens U, Distler A, Sieper J: Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis. Arthritis Rheum. 1995, 38: 499-505.CrossRefPubMed
14.
Hermann E, Fleischer B, Mayet WJ, Poralla T, Meyer zum Buschenfelde KH: Response of synovial fluid T cell clones to Yersinia enterocolitica antigens in patients with reactive Yersinia arthritis. Clin Exp Immunol. 1989, 75: 365-370.PubMedCentralPubMed
15.
Viner NJ, Bailey LC, Life PF, Bacon PA, Gaston JS: Isolation of Yersinia-specific T cell clones from the synovial membrane and synovial fluid of a patient with reactive arthritis. Arthritis Rheum. 1991, 34: 1151-1157.CrossRefPubMed
16.
Hermann E, Mayet WJ, Thomssen H, Sieper J, Poralla T, Meyer zum Buschenfelde KH, Fleischer B: HLA-DP restricted Chlamydia trachomatis specific synovial fluid T cell clones in Chlamydia-induced Reiter's disease. J Rheumatol. 1992, 19: 1243-1246.PubMed
17.
Schmidt D, Goronzy JJ, Weyand CM: CD4+CD7-CD28- T cells are expanded in rheumatoid arthritis and are characterized by autoreactivity. J Clin Invest. 1996, 97: 2027-2037.PubMedCentralCrossRefPubMed
18.
Markovic-Plese S, Cortese I, Wandinger KP, McFarland HF, Martin R: CD4+CD28- costimulation-independent T cells in multiple sclerosis. J Clin Invest. 2001, 108: 1185-1194. 10.1172/JCI200112516.PubMedCentralCrossRefPubMed
19.
Lamprecht P, Moosig F, Csernok E, Seitzer U, Schnabel A, Mueller A, Gross WL: CD28 negative T cells are enriched in granulomatous lesions of the respiratory tract in Wegener's granulomatosis. Thorax. 2001, 56: 751-757. 10.1136/thorax.56.10.751.PubMedCentralCrossRefPubMed
20.
Moosig F, Csernok E, Wang G, Gross WL: Costimulatory molecules in Wegener's granulomatosis (WG): lack of expression of CD28 and preferential up-regulation of its ligands B7-1 (CD80) and B7-2 (CD86) on T cells. Clin Exp Immunol. 1998, 114: 113-118. 10.1046/j.1365-2249.1998.00695.x.PubMedCentralCrossRefPubMed
21.
Park W, Weyand CM, Schmidt D, Goronzy JJ: Co-stimulatory pathways controlling activation and peripheral tolerance of human CD4+ CD28- T cells. Eur J Immunol. 1997, 27: 1082-1090.CrossRefPubMed
22.
Vallejo AN, Mugge LO, Klimiuk PA, Weyand CM, Goronzy JJ: Central role of thrombospondin-1 in the activation and clonal expansion of inflammatory T cells. J Immunol. 2000, 164: 2947-2954.CrossRefPubMed
23.
Namekawa T, Snyder MR, Yen JH, Goehring BE, Leibson PJ, Weyand CM, Goronzy JJ: Killer cell activating receptors function as costimulatory molecules on CD4+CD28null T cells clonally expanded in Rheumatoid Arthritis. J Immunol. 2000, 165: 1138-1145.CrossRefPubMed
24.
Yen JH, Moore BE, Nakajima T, Scholl D, Schaid DJ, Weyand CM, Goronzy JJ: Major histocompatibility complex class I recognizing receptors are disease risk genes in RA. J Exp Med. 2001, 193: 1159-1167. 10.1084/jem.193.10.1159.PubMedCentralCrossRefPubMed
25.
Snyder MR, Muegge LO, Offord C, O'Fallon WM, Bajzer Z, Weyand CM, Goronzy JJ: Formation of the killer Ig-like receptor repertoire on CD4+CD28 null T cells. J Immunol. 2002, 168: 3839-3846.CrossRefPubMed
26.
Mandelboim O, Davis DM, Reyburn HT, Vales-Gomez M, Sheu EG, Pazmany L, Strominger JL: Enhancement of class II-restricted T cell responses by co-stimulatory NK receptors for class I MHC proteins. Science. 1996, 274: 2097-2100. 10.1126/science.274.5295.2097.CrossRefPubMed
27.
van der Linden S, Valkenburg HA, Cats A: Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum. 1984, 27: 361-368.CrossRefPubMed
28.
Daltroy LH, Larson MG, Roberts NW, Liang MH: A modification of the Health Assessment Questionnaire for the spondyloarthropathies. J Rheumatol. 1990, 17: 946-950.PubMed
29.
Jenkinson TR, Mallorie PA, Whitelock HC, Kennedy LG, Garrett SL, Calin A: Defining spinal mobility in ankylosing spondylitis (AS). The Bath AS Metrology Index. J Rheumatol. 1994, 21: 1694-1698.PubMed
30.
Calin A, Garrett S, Whitelock H, Kennedy LG, O'Hea J, Mallorie P, Jenkinson T: A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index. J Rheumatol. 1994, 21: 2281-2285.PubMed
31.
Kollnberger S, Bird L, Sun MY, Retiere C, Braud VM, McMichael A, Bowness P: Cell-surface expression and immune receptor recognition of HLA-B27 homodimers. Arthritis Rheum. 2002, 46: 2972-2982. 10.1002/art.10605.CrossRefPubMed
32.
Reinhold U, Abken H: CD4+CD7- T cells: a separate subpopulation of memory T cells?. J Clin Immunol. 1997, 17: 265-271. 10.1023/A:1027318530127.CrossRefPubMed
33.
Brumbaugh KM, Perez-Villar JJ, Dick CJ, Schoon RA, Lopez-Botet M, Leibson PJ: Clonotypic differences in signaling from CD94 (kp43) on NK cells lead to divergent cellular responses. J Immunol. 1996, 157: 2804-2812.PubMed
34.
Weyand CM, Brandes JC, Schmidt D, Fulbright JW, Goronzy JJ: Functional properties of CD4+CD28- T cells in the aging immune system. Mech Ageing Dev. 1998, 102: 131-147. 10.1016/S0047-6374(97)00161-9.CrossRefPubMed
35.
O'Shea JJ, Ma A, Lipsky P: Cytokines and autoimmunity. Nat Rev Immunol. 2002, 2: 37-45. 10.1038/nri702.CrossRefPubMed
36.
Martens PB, Goronzy JJ, Schaid D, Weyand CM: Expansion of unusual CD4+ T cells in severe rheumatoid arthritis. Arthritis Rheum. 1997, 40: 1106-1114.CrossRefPubMed
37.
Brooks JM, Murray RJ, Thomas WA, Kurilla MG, Rickinson AB: Different HLA-B27 subtypes present the same immunodominant Epstein–Barr virus peptide. J Exp Med. 1993, 178: 879-887. 10.1084/jem.178.3.879.CrossRefPubMed
38.
Hooper M, Kallas EG, Coffin D, Campbell D, Evans TG, Looney RJ: Cytomegalovirus seropositivity is associated with the expansion of CD4+CD28- and CD8+CD28- T cells in rheumatoid arthritis. J Rheumatol. 1999, 26: 1452-1457.PubMed
39.
Namekawa T, Wagner UG, Goronzy JJ, Weyand CM: Functional subsets of CD4 T cells in rheumatoid synovitis. Arthritis Rheum. 1998, 41: 2108-2116. 10.1002/1529-0131(199812)41:12<2108::AID-ART5>3.3.CO;2-H.CrossRefPubMed
40.
Bix M, Locksley RM: Natural T cells. Cells that co-express NKRP-1 and TCR. J Immunol. 1995, 155: 1020-1022.PubMed
41.
Dulphy N, Rabian C, Douay C, Flinois O, Laoussadi S, Kuipers J, Tamouza R, Charron D, Toubert A: Functional modulation of expanded CD8+ synovial fluid T cells by NK cell receptor expression in HLA-B27-associated reactive arthritis. Int Immunol. 2002, 14: 471-479. 10.1093/intimm/14.5.471.CrossRefPubMed
42.
Warrington KJ, Takemura S, Goronzy JJ, Weyand CM: CD4+, CD28- T cells in rheumatoid arthritis patients combine features of the innate and adaptive immune systems. Arthritis Rheum. 2001, 44: 13-20. 10.1002/1529-0131(200101)44:1<13::AID-ANR3>3.0.CO;2-6.CrossRefPubMed
Metadata
Title
Prevalence, clinical relevance and characterization of circulating cytotoxic CD4+CD28- T cells in ankylosing spondylitis
Authors
Christina Duftner
Christian Goldberger
Albrecht Falkenbach
Reinhard Würzner
Barbara Falkensammer
Karl P Pfeiffer
Elisabeth Maerker-Hermann
Michael Schirmer
Publication date
01-10-2003
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 5/2003
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar793

Other articles of this Issue 5/2003

Arthritis Research & Therapy 5/2003 Go to the issue

Research article

An association between the acute phase response and patterns of antigen induced T cell proliferation in juvenile idiopathic arthritis

Research article

A comparative study of the inhibitory effects of interleukin-1 receptor antagonist following administration as a recombinant protein or by gene transfer

Review

A review of anabolic therapies for osteoporosis

Research article

High CXCR3 expression in synovial mast cells associated with CXCL9 and CXCL10 expression in inflammatory synovial tissues of patients with rheumatoid arthritis

Review

Ageing, autoimmunity and arthritis: An introduction

Viewpoint

Interpreting interest in interferon-α
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits