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PMID: 18704663 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Association of Graves' disease and prevalence of circulating IFN-gamma-producing CD28(-) T cells.

Journal of clinical immunology ·Vol. 28 ·No. 5 ·2008-09-00 ·Pages 464-72

Sun Z, Zhong W, Lu X, Shi B, Zhu Y, Chen L, Zhang G, Zhang X

Abstract

Peripheral blood CD4(+) and CD8(+) T-cell subsets lacking surface CD28 have been suggested to predispose patients to immune-mediated disorders. To determine the role of CD28(-) T-cell subset in Graves' disease (GD), we characterized peripheral blood CD4(+)CD28(-) and CD8(+)CD28(-) T cell from early onset GD patients. GD patients had significantly higher percentages of CD4(+)CD28(-) and CD8(+)CD28(-) T cells than did healthy donors. Both CD28(-) T cells expressed mostly CD45RO, suggesting that they are activated and/or are memory T cells. GD patient-derived CD4(+)CD28(-) and CD8(+)CD28(-) T cells produced more intracellular IFN-gamma than their counterparts from healthy donors. Furthermore, CD4(+)CD28(-) and CD8(+)CD28(-) T cells from GD patients with Graves' ophthalmopathy (GO) secreted higher level of intracellular IFN-gamma than those CD28(-) T cells from GD patients without GO. Retrospective analysis showed that the increased levels of CD4(+)CD28(-) T cells and their IFN-gamma-producing subgroups were positively correlated to the serum anti-thyrotropin receptor (TSHR) autoantibodies (TRAb). Our observations suggest that increased IFN-gamma-producing CD28(-) T cells in GD patients may play an important role in the pathogenesis of GD.

MeSH Terms
Adult Autoantibodies/blood CD28 Antigens CD4-Positive T-Lymphocytes/immunology,metabolism CD8-Positive T-Lymphocytes/immunology,metabolism Cell Separation Female Flow Cytometry Graves Ophthalmopathy/blood,genetics,immunology Humans Immunologic Memory/genetics Interferon-gamma/genetics,immunology,metabolism Interleukin-2/metabolism Interleukin-4/metabolism Leukocyte Common Antigens/biosynthesis,genetics Male Middle Aged Receptors, Thyrotropin/immunology Retrospective Studies Statistics as Topic T-Lymphocyte Subsets/immunology,metabolism
Chemicals
Autoantibodies CD28 Antigens Interleukin-2 Receptors, Thyrotropin Interleukin-4 Interferon-gamma Leukocyte Common Antigens
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Sun Zhiping
Medical Biotechnology Institute, Soochow University, 48 Renmin Road, Suzhou 215007, China.
Zhong Weixue
Lu Xiang
Shi Bimin
Zhu Yibei
Chen Lei
Zhang Guangbo
Zhang Xueguang
References (39)
39 references, click to expand
  1. Naked TSH receptor DNA vaccination: A TH1 T cell response in which interferon-gamma production, rather than antibody, dominates the immune response in mice.
    Endocrinology. 2001 Aug;142(8):3530-6 PMID: 11459799
  2. Prevalence, clinical relevance and characterization of circulating cytotoxic CD4+CD28- T cells in ankylosing spondylitis.
    Arthritis Res Ther. 2003;5(5):R292-300 PMID: 12932293
  3. Interferon-gamma deficiency prevents coronary arteriosclerosis but not myocardial rejection in transplanted mouse hearts.
    J Clin Invest. 1997 Aug 1;100(3):550-7 PMID: 9239401
  4. Down-regulation of CD28 expression by TNF-alpha.
    J Immunol. 2001 Sep 15;167(6):3231-8 PMID: 11544310
  5. The B7-CD28 superfamily.
    Nat Rev Immunol. 2002 Feb;2(2):116-26 PMID: 11910893
  6. CD4+ CD7- CD28- T cells are expanded in rheumatoid arthritis and are characterized by autoreactivity.
    J Clin Invest. 1996 May 1;97(9):2027-37 PMID: 8621791
  7. The CD28 signaling pathway regulates glucose metabolism.
    Immunity. 2002 Jun;16(6):769-77 PMID: 12121659
  8. Downregulation of CD28 surface antigen on CD4+ and CD8+ T lymphocytes during HIV-1 infection.
    J Acquir Immune Defic Syndr (1988). 1994 Mar;7(3):245-53 PMID: 7906302
  9. The pathogenesis of Graves' disease.
    Endocrinol Metab Clin North Am. 1998 Mar;27(1):73-89 PMID: 9534029
  10. Peripheral blood and granuloma CD4(+)CD28(-) T cells are a major source of interferon-gamma and tumor necrosis factor-alpha in Wegener's granulomatosis.
    Am J Pathol. 2002 May;160(5):1717-24 PMID: 12000723
  11. Intrathyroidal cytokine gene expression profiles in autoimmune thyroiditis.
    J Endocrinol. 1994 May;141(2):309-15 PMID: 8046301
  12. Modulation of CD28 expression: distinct regulatory pathways during activation and replicative senescence.
    J Immunol. 1999 Jun 1;162(11):6572-9 PMID: 10352273
  13. CD28-negative cytolytic effector T cells frequently express NK receptors and are present at variable proportions in circulating lymphocytes from healthy donors and melanoma patients.
    Eur J Immunol. 1999 Jun;29(6):1990-9 PMID: 10382762
  14. Naive and effector CD4 T cells differ in their requirements for T cell receptor versus costimulatory signals.
    J Immunol. 1996 Oct 15;157(8):3280-9 PMID: 8871622
  15. CD28 negative T cells are enriched in granulomatous lesions of the respiratory tract in Wegener's granulomatosis.
    Thorax. 2001 Oct;56(10):751-7 PMID: 11562512
  16. CD28/B7 interactions deliver a unique signal to naive T cells that regulates cell survival but not early proliferation.
    J Immunol. 1996 Nov 1;157(9):3909-17 PMID: 8892622
  17. Postthymic development of CD28-CD8+ T cell subset: age-associated expansion and shift from memory to naive phenotype.
    J Immunol. 1999 Mar 15;162(6):3327-35 PMID: 10092786
  18. Insight into Graves' hyperthyroidism from animal models.
    Endocr Rev. 2005 Oct;26(6):800-32 PMID: 15827111
  19. Lack of B7-1/BB1 and B7-2/B70 expression on thyrocytes of patients with Graves' disease. Delivery of costimulatory signals from bystander professional antigen-presenting cells.
    J Clin Endocrinol Metab. 1996 Nov;81(11):4137-43 PMID: 8923872
  20. Perturbation of the T-cell repertoire in patients with unstable angina.
    Circulation. 1999 Nov 23;100(21):2135-9 PMID: 10571971
  21. Immune deviation away from Th1 in interferon-gamma knockout mice does not enhance TSH receptor antibody production after naked DNA vaccination.
    Endocrinology. 2002 Apr;143(4):1182-9 PMID: 11897670
  22. Immunological memory.
    Curr Opin Immunol. 1997 Jun;9(3):371-9 PMID: 9203411
  23. Human T-cell clones from autoimmune thyroid glands: specific recognition of autologous thyroid cells.
    Science. 1985 Apr 5;228(4695):85-9 PMID: 3871967
  24. Prevention of autoantibody-mediated Graves'-like hyperthyroidism in mice with IL-4, a Th2 cytokine.
    J Immunol. 2003 Apr 1;170(7):3522-7 PMID: 12646613
  25. Killer cell activating receptors function as costimulatory molecules on CD4+CD28null T cells clonally expanded in rheumatoid arthritis.
    J Immunol. 2000 Jul 15;165(2):1138-45 PMID: 10878393
  26. Chronic autoimmune thyroiditis.
    N Engl J Med. 1996 Jul 11;335(2):99-107 PMID: 8649497
  27. Relative overexpression of macrophage-derived cytokines in orbital adipose tissue from patients with graves' ophthalmopathy.
    J Clin Endocrinol Metab. 2003 Sep;88(9):4246-50 PMID: 12970294
  28. Current perspective on the pathogenesis of Graves' disease and ophthalmopathy.
    Endocr Rev. 2003 Dec;24(6):802-35 PMID: 14671007
  29. Etiopathogenesis of Graves' disease.
    Neuro Endocrinol Lett. 2003 Jun-Aug;24(3-4):161-6 PMID: 14523350
  30. Expanded T cell populations in patients with Wegener's granulomatosis: characteristics and correlates with disease activity.
    J Clin Immunol. 1998 Nov;18(6):404-13 PMID: 9857285
  31. Emergence of a CD4+CD28- granzyme B+, cytomegalovirus-specific T cell subset after recovery of primary cytomegalovirus infection.
    J Immunol. 2004 Aug 1;173(3):1834-41 PMID: 15265915
  32. The thyrotropin (TSH) receptor: interaction with TSH and autoantibodies.
    Endocr Rev. 1998 Dec;19(6):673-716 PMID: 9861544
  33. Aging-related deficiency of CD28 expression in CD4+ T cells is associated with the loss of gene-specific nuclear factor binding activity.
    J Biol Chem. 1998 Apr 3;273(14):8119-29 PMID: 9525915
  34. Autoantigen recognition by thyroid-infiltrating T cells in Graves disease.
    Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7415-9 PMID: 1714602
  35. Expression and kinetics of cytokines determined by intracellular staining using flow cytometry.
    J Immunol Methods. 1999 Feb 1;223(1):115-21 PMID: 10037239
  36. CD4+CD28- costimulation-independent T cells in multiple sclerosis.
    J Clin Invest. 2001 Oct;108(8):1185-94 PMID: 11602626
  37. The study of visual evoked potentials in patients with thyroid-associated ophthalmopathy identifies asymptomatic optic nerve involvement.
    J Clin Endocrinol Metab. 1997 Apr;82(4):1027-30 PMID: 9100568
  38. Co-stimulatory pathways controlling activation and peripheral tolerance of human CD4+CD28- T cells.
    Eur J Immunol. 1997 May;27(5):1082-90 PMID: 9174596
  39. High prevalence of circulating CD4+CD28- T-cells in patients with small abdominal aortic aneurysms.
    Arterioscler Thromb Vasc Biol. 2005 Jul;25(7):1347-52 PMID: 15845908
Article Info
Journal
Journal of clinical immunology
Abbr.
J Clin Immunol
ISSN
0271-9142
DOI
10.1007/s10875-008-9213-4
Published
2008-09-00
Epub
2008-00-14
Pages
464-72
Language
English
Region
Netherlands
NLM ID
8102137
Subset
IM
External Links
PubMed source DOI: 10.1007/s10875-008-9213-4 View journal details
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