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Erschienen in: Immunologic Research 2-3/2011

01.08.2011 | UNIVERSITY OF PITTSBURGH IMMUNOLOGY 2011

CD8+ T cells in systemic sclerosis

verfasst von: Patrizia Fuschiotti

Erschienen in: Immunologic Research | Ausgabe 2-3/2011

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Abstract

Systemic sclerosis (SSc) is a progressive and highly debilitating autoimmune disorder characterized by inflammation, fibrosis, and vascular damage of the connective tissue. T cell-derived cytokines have been implicated in the induction of fibrosis. We found that high levels of the profibrotic type-2 cytokine IL-13 are produced by peripheral blood effector CD8+ T cells from SSc patients compared to normal controls. This abnormality correlates with increased expression of the transcription factor GATA-3 and the extent of skin fibrosis. Together, the data provide new insights into SSc pathogenesis and identify a specific T cell phenotype that can be used as a biomarker of immune dysfunction in patients with SSc and as a novel therapeutic target for this currently incurable disease.
Literatur
1.
Zurück zum Zitat Varga J, Abraham D. Systemic sclerosis: a prototypic multisystem fibrotic disorder. J Clin Invest. 2007;117(3):557–67.PubMedCrossRef Varga J, Abraham D. Systemic sclerosis: a prototypic multisystem fibrotic disorder. J Clin Invest. 2007;117(3):557–67.PubMedCrossRef
3.
Zurück zum Zitat Arnett FC, Cho M, Chatterjee S, Aguilar MB, Reveille JD, Mayes MD. Familial occurrence frequencies and relative risks for systemic sclerosis (scleroderma) in three United States cohorts. Arthritis Rheum. 2001;44(6):1359–62.PubMedCrossRef Arnett FC, Cho M, Chatterjee S, Aguilar MB, Reveille JD, Mayes MD. Familial occurrence frequencies and relative risks for systemic sclerosis (scleroderma) in three United States cohorts. Arthritis Rheum. 2001;44(6):1359–62.PubMedCrossRef
4.
Zurück zum Zitat Pandey JP, LeRoy EC. Human cytomegalovirus and the vasculopathies of autoimmune diseases (especially scleroderma), allograft rejection, and coronary restenosis. Arthritis Rheum. 1998;41(1):10–5.PubMedCrossRef Pandey JP, LeRoy EC. Human cytomegalovirus and the vasculopathies of autoimmune diseases (especially scleroderma), allograft rejection, and coronary restenosis. Arthritis Rheum. 1998;41(1):10–5.PubMedCrossRef
5.
Zurück zum Zitat Nietert PJ, Silver RM. Systemic sclerosis: environmental and occupational risk factors. Curr Opin Rheumatol. 2000;12(6):520–6.PubMedCrossRef Nietert PJ, Silver RM. Systemic sclerosis: environmental and occupational risk factors. Curr Opin Rheumatol. 2000;12(6):520–6.PubMedCrossRef
6.
Zurück zum Zitat Medsger TA Jr. Classification, prognosis. In: Clements PJ, Furst DE, editors. Systemic sclerosis. 2nd ed. Philadelphia: Lippincott Williams & Williams; 2004. p. 17–28. Medsger TA Jr. Classification, prognosis. In: Clements PJ, Furst DE, editors. Systemic sclerosis. 2nd ed. Philadelphia: Lippincott Williams & Williams; 2004. p. 17–28.
7.
Zurück zum Zitat Denton CP, Lindahl GE, Khan K, Shiwen X, Ong VH, Gaspar NJ, et al. Activation of key profibrotic mechanisms in transgenic fibroblasts expressing kinase-deficient type II Transforming growth factor-{beta} receptor (T{beta}RII{delta}k). J Biol Chem. 2005;280(16):16053–65.PubMedCrossRef Denton CP, Lindahl GE, Khan K, Shiwen X, Ong VH, Gaspar NJ, et al. Activation of key profibrotic mechanisms in transgenic fibroblasts expressing kinase-deficient type II Transforming growth factor-{beta} receptor (T{beta}RII{delta}k). J Biol Chem. 2005;280(16):16053–65.PubMedCrossRef
8.
Zurück zum Zitat Kahaleh MB. Raynaud phenomenon and the vascular disease in scleroderma. Curr Opin Rheumatol. 2004;16(6):718–22.PubMedCrossRef Kahaleh MB. Raynaud phenomenon and the vascular disease in scleroderma. Curr Opin Rheumatol. 2004;16(6):718–22.PubMedCrossRef
9.
Zurück zum Zitat Jimenez SA, Derk CT. Following the molecular pathways toward an understanding of the pathogenesis of systemic sclerosis. Ann Intern Med. 2004;140(1):37–50.PubMed Jimenez SA, Derk CT. Following the molecular pathways toward an understanding of the pathogenesis of systemic sclerosis. Ann Intern Med. 2004;140(1):37–50.PubMed
10.
Zurück zum Zitat Sakkas LI, Platsoucas CD. Is systemic sclerosis an antigen-driven T cell disease? Arthritis Rheum. 2004;50(6):1721–33.PubMedCrossRef Sakkas LI, Platsoucas CD. Is systemic sclerosis an antigen-driven T cell disease? Arthritis Rheum. 2004;50(6):1721–33.PubMedCrossRef
11.
Zurück zum Zitat Prescott RJ, Freemont AJ, Jones CJ, Hoyland J, Fielding P. Sequential dermal microvascular and perivascular changes in the development of scleroderma. J Pathol. 1992;166(3):255–63.PubMedCrossRef Prescott RJ, Freemont AJ, Jones CJ, Hoyland J, Fielding P. Sequential dermal microvascular and perivascular changes in the development of scleroderma. J Pathol. 1992;166(3):255–63.PubMedCrossRef
12.
Zurück zum Zitat Roumm AD, Whiteside TL, Medsger TA Jr, Rodnan GP. Lymphocytes in the skin of patients with progressive systemic sclerosis. Quantification, subtyping, and clinical correlations. Arthritis Rheum. 1984;27(6):645–53.PubMedCrossRef Roumm AD, Whiteside TL, Medsger TA Jr, Rodnan GP. Lymphocytes in the skin of patients with progressive systemic sclerosis. Quantification, subtyping, and clinical correlations. Arthritis Rheum. 1984;27(6):645–53.PubMedCrossRef
13.
Zurück zum Zitat Fleischmajer R, Perlish JS, Reeves JR. Cellular infiltrates in scleroderma skin. Arthritis Rheum. 1977;20(4):975–84.PubMedCrossRef Fleischmajer R, Perlish JS, Reeves JR. Cellular infiltrates in scleroderma skin. Arthritis Rheum. 1977;20(4):975–84.PubMedCrossRef
14.
Zurück zum Zitat Giacomelli R, Matucci-Cerinic M, Cipriani P, Ghersetich I, Lattanzio R, Pavan A, et al. Circulating Vdelta1+ T cells are activated and accumulate in the skin of systemic sclerosis patients. Arthritis Rheum. 1998;41(2):327–34.PubMedCrossRef Giacomelli R, Matucci-Cerinic M, Cipriani P, Ghersetich I, Lattanzio R, Pavan A, et al. Circulating Vdelta1+ T cells are activated and accumulate in the skin of systemic sclerosis patients. Arthritis Rheum. 1998;41(2):327–34.PubMedCrossRef
15.
Zurück zum Zitat Fiocco U, Rosada M, Cozzi L, Ortolani C, De Silvestro G, Ruffatti A, et al. Early phenotypic activation of circulating helper memory T cells in scleroderma: correlation with disease activity. Ann Rheum Dis. 1993;52(4):272–7.PubMedCrossRef Fiocco U, Rosada M, Cozzi L, Ortolani C, De Silvestro G, Ruffatti A, et al. Early phenotypic activation of circulating helper memory T cells in scleroderma: correlation with disease activity. Ann Rheum Dis. 1993;52(4):272–7.PubMedCrossRef
16.
Zurück zum Zitat Wells AU, Lorimer S, Majumdar S, Harrison NK, Corrin B, Black CM, et al. Fibrosing alveolitis in systemic sclerosis: increase in memory T-cells in lung interstitium. Eur Respir J. 1995;8(2):266–71.PubMedCrossRef Wells AU, Lorimer S, Majumdar S, Harrison NK, Corrin B, Black CM, et al. Fibrosing alveolitis in systemic sclerosis: increase in memory T-cells in lung interstitium. Eur Respir J. 1995;8(2):266–71.PubMedCrossRef
17.
Zurück zum Zitat Harmancy E, Gulbas Z, Ozdemir N, Elbek O, Mutlu S, Kolsuz M, et al. T lymphocyte activation in bronchoalveolar lavage of patients with interstitial lung disease. Allerg Immunol (Paris). 1998;30(8):259–61. Harmancy E, Gulbas Z, Ozdemir N, Elbek O, Mutlu S, Kolsuz M, et al. T lymphocyte activation in bronchoalveolar lavage of patients with interstitial lung disease. Allerg Immunol (Paris). 1998;30(8):259–61.
18.
Zurück zum Zitat Kahari VM, Sandberg M, Kalimo H, Vuorio T, Vuorio E. Identification of fibroblasts responsible for increased collagen production in localized scleroderma by in situ hybridization. J Invest Dermatol. 1988;90(5):664–70.PubMedCrossRef Kahari VM, Sandberg M, Kalimo H, Vuorio T, Vuorio E. Identification of fibroblasts responsible for increased collagen production in localized scleroderma by in situ hybridization. J Invest Dermatol. 1988;90(5):664–70.PubMedCrossRef
19.
Zurück zum Zitat Sakkas LI, Xu B, Artlett CM, Lu S, Jimenez SA, Platsoucas CD. Oligoclonal T cell expansion in the skin of patients with systemic sclerosis. J Immunol. 2002;168(7):3649–59.PubMed Sakkas LI, Xu B, Artlett CM, Lu S, Jimenez SA, Platsoucas CD. Oligoclonal T cell expansion in the skin of patients with systemic sclerosis. J Immunol. 2002;168(7):3649–59.PubMed
20.
Zurück zum Zitat Denton CP, Abraham DJ. Transforming growth factor-beta and connective tissue growth factor: key cytokines in scleroderma pathogenesis. Curr Opin Rheumatol. 2001;13(6):505–11.PubMedCrossRef Denton CP, Abraham DJ. Transforming growth factor-beta and connective tissue growth factor: key cytokines in scleroderma pathogenesis. Curr Opin Rheumatol. 2001;13(6):505–11.PubMedCrossRef
21.
Zurück zum Zitat Sato S, Hasegawa M, Takehara K. Serum levels of interleukin-6 and interleukin-10 correlate with total skin thickness score in patients with systemic sclerosis. J Dermatol Sci. 2001;27(2):140–6.PubMedCrossRef Sato S, Hasegawa M, Takehara K. Serum levels of interleukin-6 and interleukin-10 correlate with total skin thickness score in patients with systemic sclerosis. J Dermatol Sci. 2001;27(2):140–6.PubMedCrossRef
22.
Zurück zum Zitat Kurasawa K, Hirose K, Sano H, Endo H, Shinkai H, Nawata Y, et al. Increased interleukin-17 production in patients with systemic sclerosis. Arthritis Rheum. 2000;43(11):2455–63.PubMedCrossRef Kurasawa K, Hirose K, Sano H, Endo H, Shinkai H, Nawata Y, et al. Increased interleukin-17 production in patients with systemic sclerosis. Arthritis Rheum. 2000;43(11):2455–63.PubMedCrossRef
23.
Zurück zum Zitat Hasegawa M, Fujimoto M, Kikuchi K, Takehara K. Elevated serum levels of interleukin 4 (IL-4), IL-10, and IL-13 in patients with systemic sclerosis. J Rheumatol. 1997;24(2):328–32.PubMed Hasegawa M, Fujimoto M, Kikuchi K, Takehara K. Elevated serum levels of interleukin 4 (IL-4), IL-10, and IL-13 in patients with systemic sclerosis. J Rheumatol. 1997;24(2):328–32.PubMed
24.
Zurück zum Zitat Fertin C, Nicolas JF, Gillery P, Kalis B, Banchereau J, Maquart FX. Interleukin-4 stimulates collagen synthesis by normal and scleroderma fibroblasts in dermal equivalents. Cell Mol Biol. 1991;37(8):823–9.PubMed Fertin C, Nicolas JF, Gillery P, Kalis B, Banchereau J, Maquart FX. Interleukin-4 stimulates collagen synthesis by normal and scleroderma fibroblasts in dermal equivalents. Cell Mol Biol. 1991;37(8):823–9.PubMed
25.
Zurück zum Zitat Kuwana M, Medsger TA Jr, Wright TM. T and B cell collaboration is essential for the autoantibody response to DNA topoisomerase I in systemic sclerosis. J Immunol. 1995;155(5):2703–14.PubMed Kuwana M, Medsger TA Jr, Wright TM. T and B cell collaboration is essential for the autoantibody response to DNA topoisomerase I in systemic sclerosis. J Immunol. 1995;155(5):2703–14.PubMed
26.
27.
28.
29.
Zurück zum Zitat Mosmann TR, Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today. 1996;17(3):138–46.PubMedCrossRef Mosmann TR, Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today. 1996;17(3):138–46.PubMedCrossRef
30.
Zurück zum Zitat Hoffmann KF, McCarty TC, Segal DH, Chiaramonte M, Hesse M, Davis EM, et al. Disease fingerprinting with cDNA microarrays reveals distinct gene expression profiles in lethal type 1 and type 2 cytokine-mediated inflammatory reactions. Faseb J. 2001;15(13):2545–7.PubMed Hoffmann KF, McCarty TC, Segal DH, Chiaramonte M, Hesse M, Davis EM, et al. Disease fingerprinting with cDNA microarrays reveals distinct gene expression profiles in lethal type 1 and type 2 cytokine-mediated inflammatory reactions. Faseb J. 2001;15(13):2545–7.PubMed
31.
Zurück zum Zitat Sandler NG, Mentink-Kane MM, Cheever AW, Wynn TA. Global gene expression profiles during acute pathogen-induced pulmonary inflammation reveal divergent roles for Th1 and Th2 responses in tissue repair. J Immunol. 2003;171(7):3655–67.PubMed Sandler NG, Mentink-Kane MM, Cheever AW, Wynn TA. Global gene expression profiles during acute pathogen-induced pulmonary inflammation reveal divergent roles for Th1 and Th2 responses in tissue repair. J Immunol. 2003;171(7):3655–67.PubMed
32.
Zurück zum Zitat Lakos G, Melichian D, Wu M, Varga J. Increased bleomycin-induced skin fibrosis in mice lacking the Th1-specific transcription factor T-bet. Pathobiology. 2006;73(5):224–37.PubMedCrossRef Lakos G, Melichian D, Wu M, Varga J. Increased bleomycin-induced skin fibrosis in mice lacking the Th1-specific transcription factor T-bet. Pathobiology. 2006;73(5):224–37.PubMedCrossRef
33.
Zurück zum Zitat Aliprantis AO, Wang J, Fathman JW, Lemaire R, Dorfman DM, Lafyatis R, et al. Transcription factor T-bet regulates skin sclerosis through its function in innate immunity and via IL-13. Proc Natl Acad Sci USA. 2007;104(8):2827–30.PubMedCrossRef Aliprantis AO, Wang J, Fathman JW, Lemaire R, Dorfman DM, Lafyatis R, et al. Transcription factor T-bet regulates skin sclerosis through its function in innate immunity and via IL-13. Proc Natl Acad Sci USA. 2007;104(8):2827–30.PubMedCrossRef
34.
Zurück zum Zitat Tsuji-Yamada J, Nakazawa M, Minami M, Sasaki T. Increased frequency of interleukin 4 producing CD4+ and CD8+ cells in peripheral blood from patients with systemic sclerosis. J Rheumatol. 2001;28(6):1252–8.PubMed Tsuji-Yamada J, Nakazawa M, Minami M, Sasaki T. Increased frequency of interleukin 4 producing CD4+ and CD8+ cells in peripheral blood from patients with systemic sclerosis. J Rheumatol. 2001;28(6):1252–8.PubMed
35.
Zurück zum Zitat Mavalia C, Scaletti C, Romagnani P, Carossino AM, Pignone A, Emmi L, et al. Type 2 helper T-cell predominance and high CD30 expression in systemic sclerosis. Am J Pathol. 1997;151(6):1751–8.PubMed Mavalia C, Scaletti C, Romagnani P, Carossino AM, Pignone A, Emmi L, et al. Type 2 helper T-cell predominance and high CD30 expression in systemic sclerosis. Am J Pathol. 1997;151(6):1751–8.PubMed
36.
Zurück zum Zitat Atamas SP, Yurovsky VV, Wise R, Wigley FM, Goter Robinson CJ, Henry P, et al. Production of type 2 cytokines by CD8+ lung cells is associated with greater decline in pulmonary function in patients with systemic sclerosis. Arthritis Rheum. 1999;42(6):1168–78.PubMedCrossRef Atamas SP, Yurovsky VV, Wise R, Wigley FM, Goter Robinson CJ, Henry P, et al. Production of type 2 cytokines by CD8+ lung cells is associated with greater decline in pulmonary function in patients with systemic sclerosis. Arthritis Rheum. 1999;42(6):1168–78.PubMedCrossRef
37.
Zurück zum Zitat Fujii H, Hasegawa M, Takehara K, Mukaida N, Sato S. Abnormal expression of intracellular cytokines and chemokine receptors in peripheral blood T lymphocytes from patients with systemic sclerosis. Clin Exp Immunol. 2002;130(3):548–56.PubMedCrossRef Fujii H, Hasegawa M, Takehara K, Mukaida N, Sato S. Abnormal expression of intracellular cytokines and chemokine receptors in peripheral blood T lymphocytes from patients with systemic sclerosis. Clin Exp Immunol. 2002;130(3):548–56.PubMedCrossRef
38.
Zurück zum Zitat Valentini G, Baroni A, Esposito K, Naclerio C, Buommino E, Farzati A, et al. Peripheral blood T lymphocytes from systemic sclerosis patients show both Th1 and Th2 activation. J Clin Immunol. 2001;21(3):210–7.PubMedCrossRef Valentini G, Baroni A, Esposito K, Naclerio C, Buommino E, Farzati A, et al. Peripheral blood T lymphocytes from systemic sclerosis patients show both Th1 and Th2 activation. J Clin Immunol. 2001;21(3):210–7.PubMedCrossRef
39.
Zurück zum Zitat Atamas SP, White B. Cytokine regulation of pulmonary fibrosis in scleroderma. Cytokine Growth Factor Rev. 2003;14(6):537–50.PubMedCrossRef Atamas SP, White B. Cytokine regulation of pulmonary fibrosis in scleroderma. Cytokine Growth Factor Rev. 2003;14(6):537–50.PubMedCrossRef
40.
Zurück zum Zitat Fuschiotti P, Medsger TA Jr, Morel PA. Effector CD8+ T cells in systemic sclerosis patients produce abnormally high levels of interleukin-13 associated with increased skin fibrosis. Arthritis Rheum. 2009;60(4):1119–28.PubMedCrossRef Fuschiotti P, Medsger TA Jr, Morel PA. Effector CD8+ T cells in systemic sclerosis patients produce abnormally high levels of interleukin-13 associated with increased skin fibrosis. Arthritis Rheum. 2009;60(4):1119–28.PubMedCrossRef
41.
Zurück zum Zitat Riccieri V, Rinaldi T, Spadaro A, Scrivo R, Ceccarelli F, Franco MD, et al. Interleukin-13 in systemic sclerosis: relationship to nailfold capillaroscopy abnormalities. Clin Rheumatol. 2003;22(2):102–6.PubMedCrossRef Riccieri V, Rinaldi T, Spadaro A, Scrivo R, Ceccarelli F, Franco MD, et al. Interleukin-13 in systemic sclerosis: relationship to nailfold capillaroscopy abnormalities. Clin Rheumatol. 2003;22(2):102–6.PubMedCrossRef
42.
Zurück zum Zitat Fichtner-Feigl S, Strober W, Kawakami K, Puri RK, Kitani A. IL-13 signaling through the IL-13alpha2 receptor is involved in induction of TGF-beta1 production and fibrosis. Nat Med. 2006;12(1):99–106.PubMedCrossRef Fichtner-Feigl S, Strober W, Kawakami K, Puri RK, Kitani A. IL-13 signaling through the IL-13alpha2 receptor is involved in induction of TGF-beta1 production and fibrosis. Nat Med. 2006;12(1):99–106.PubMedCrossRef
43.
Zurück zum Zitat Lee CG, Homer RJ, Zhu Z, Lanone S, Wang X, Koteliansky V, et al. Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor beta(1). J Exp Med. 2001;194(6):809–21.PubMedCrossRef Lee CG, Homer RJ, Zhu Z, Lanone S, Wang X, Koteliansky V, et al. Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor beta(1). J Exp Med. 2001;194(6):809–21.PubMedCrossRef
44.
Zurück zum Zitat Zhu Z, Homer RJ, Wang Z, Chen Q, Geba GP, Wang J, et al. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest. 1999;103(6):779–88.PubMedCrossRef Zhu Z, Homer RJ, Wang Z, Chen Q, Geba GP, Wang J, et al. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest. 1999;103(6):779–88.PubMedCrossRef
45.
46.
Zurück zum Zitat Wills-Karp M, Finkelman FD. Untangling the complex web of IL-4- and IL-13-mediated signaling pathways. Sci Signal. 2008;1(51):pe55.PubMedCrossRef Wills-Karp M, Finkelman FD. Untangling the complex web of IL-4- and IL-13-mediated signaling pathways. Sci Signal. 2008;1(51):pe55.PubMedCrossRef
47.
Zurück zum Zitat Andrew DP, Chang MS, McNinch J, Wathen ST, Rihanek M, Tseng J, et al. STCP-1 (MDC) CC chemokine acts specifically on chronically activated Th2 lymphocytes and is produced by monocytes on stimulation with Th2 cytokines IL-4 and IL-13. J Immunol. 1998;161(9):5027–38.PubMed Andrew DP, Chang MS, McNinch J, Wathen ST, Rihanek M, Tseng J, et al. STCP-1 (MDC) CC chemokine acts specifically on chronically activated Th2 lymphocytes and is produced by monocytes on stimulation with Th2 cytokines IL-4 and IL-13. J Immunol. 1998;161(9):5027–38.PubMed
48.
Zurück zum Zitat Falkner D, Wilson J, Fertig N, Clawson K, Medsger TA Jr, Morel PA. Studies of HLA-DR and DQ alleles in systemic sclerosis patients with autoantibodies to RNA polymerases and U3-RNP (fibrillarin). J Rheumatol. 2000;27(5):1196–202.PubMed Falkner D, Wilson J, Fertig N, Clawson K, Medsger TA Jr, Morel PA. Studies of HLA-DR and DQ alleles in systemic sclerosis patients with autoantibodies to RNA polymerases and U3-RNP (fibrillarin). J Rheumatol. 2000;27(5):1196–202.PubMed
49.
Zurück zum Zitat Johnson RW, Tew MB, Arnett FC. The genetics of systemic sclerosis. Curr Rheumatol Rep. 2002;4(2):99–107.PubMedCrossRef Johnson RW, Tew MB, Arnett FC. The genetics of systemic sclerosis. Curr Rheumatol Rep. 2002;4(2):99–107.PubMedCrossRef
50.
Zurück zum Zitat Ercole LP, Malvezzi M, Boaretti AC, Utiyama SR, Rachid A. Analysis of lymphocyte subpopulations in systemic sclerosis. J Investig Allergol Clin Immunol. 2003;13(2):87–93.PubMed Ercole LP, Malvezzi M, Boaretti AC, Utiyama SR, Rachid A. Analysis of lymphocyte subpopulations in systemic sclerosis. J Investig Allergol Clin Immunol. 2003;13(2):87–93.PubMed
51.
Zurück zum Zitat Gambichler T, Tigges C, Burkert B, Hoxtermann S, Altmeyer P, Kreuter A. Absolute count of T and B lymphocyte subsets is decreased in systemic sclerosis. Eur J Med Res. 2010;15(1):44–6.PubMed Gambichler T, Tigges C, Burkert B, Hoxtermann S, Altmeyer P, Kreuter A. Absolute count of T and B lymphocyte subsets is decreased in systemic sclerosis. Eur J Med Res. 2010;15(1):44–6.PubMed
52.
Zurück zum Zitat Yurovsky VV, Wigley FM, Wise RA, White B. Skewing of the CD8+ T-cell repertoire in the lungs of patients with systemic sclerosis. Hum Immunol. 1996;48(1–2):84–97.PubMedCrossRef Yurovsky VV, Wigley FM, Wise RA, White B. Skewing of the CD8+ T-cell repertoire in the lungs of patients with systemic sclerosis. Hum Immunol. 1996;48(1–2):84–97.PubMedCrossRef
53.
Zurück zum Zitat Luzina IG, Atamas SP, Wise R, Wigley FM, Choi J, Xiao HQ, et al. Occurrence of an activated, profibrotic pattern of gene expression in lung CD8+ T cells from scleroderma patients. Arthritis Rheum. 2003;48(8):2262–74.PubMedCrossRef Luzina IG, Atamas SP, Wise R, Wigley FM, Choi J, Xiao HQ, et al. Occurrence of an activated, profibrotic pattern of gene expression in lung CD8+ T cells from scleroderma patients. Arthritis Rheum. 2003;48(8):2262–74.PubMedCrossRef
54.
Zurück zum Zitat Takata H, Takiguchi M. Three memory subsets of human CD8+ T cells differently expressing three cytolytic effector molecules. J Immunol. 2006;177(7):4330–40.PubMed Takata H, Takiguchi M. Three memory subsets of human CD8+ T cells differently expressing three cytolytic effector molecules. J Immunol. 2006;177(7):4330–40.PubMed
55.
Zurück zum Zitat Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature. 1999;401(6754):708–12.PubMedCrossRef Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature. 1999;401(6754):708–12.PubMedCrossRef
56.
Zurück zum Zitat Miyahara N, Swanson BJ, Takeda K, Taube C, Miyahara S, Kodama T, et al. Effector CD8+ T cells mediate inflammation and airway hyper-responsiveness. Nat Med. 2004;10(8):865–9.PubMedCrossRef Miyahara N, Swanson BJ, Takeda K, Taube C, Miyahara S, Kodama T, et al. Effector CD8+ T cells mediate inflammation and airway hyper-responsiveness. Nat Med. 2004;10(8):865–9.PubMedCrossRef
57.
Zurück zum Zitat Casciola-Rosen L, Andrade F, Ulanet D, Wong WB, Rosen A. Cleavage by granzyme B is strongly predictive of autoantigen status: implications for initiation of autoimmunity. J Exp Med. 1999;190(6):815–26.PubMedCrossRef Casciola-Rosen L, Andrade F, Ulanet D, Wong WB, Rosen A. Cleavage by granzyme B is strongly predictive of autoantigen status: implications for initiation of autoimmunity. J Exp Med. 1999;190(6):815–26.PubMedCrossRef
58.
Zurück zum Zitat Kahaleh MB, Fan PS. Mechanism of serum-mediated endothelial injury in scleroderma: identification of a granular enzyme in scleroderma skin and sera. Clin Immunol Immunopathol. 1997;83(1):32–40.PubMedCrossRef Kahaleh MB, Fan PS. Mechanism of serum-mediated endothelial injury in scleroderma: identification of a granular enzyme in scleroderma skin and sera. Clin Immunol Immunopathol. 1997;83(1):32–40.PubMedCrossRef
59.
Zurück zum Zitat Medsger TA, Jr., Ivanco DE, Kardava L, Morel PA, Lucas MR, Fuschiotti P. GATA-3 upregulation in CD8+ T cells is a biomarker of immune dysfunction in systemic sclerosis, resulting in excess IL-13 production. Arthritis Rheum. 2011;63:1738–47.PubMedCrossRef Medsger TA, Jr., Ivanco DE, Kardava L, Morel PA, Lucas MR, Fuschiotti P. GATA-3 upregulation in CD8+ T cells is a biomarker of immune dysfunction in systemic sclerosis, resulting in excess IL-13 production. Arthritis Rheum. 2011;63:1738–47.PubMedCrossRef
Metadaten
Titel
CD8+ T cells in systemic sclerosis
verfasst von
Patrizia Fuschiotti
Publikationsdatum
01.08.2011
Verlag
Humana Press Inc
Erschienen in
Immunologic Research / Ausgabe 2-3/2011
Print ISSN: 0257-277X
Elektronische ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-011-8222-1

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