Increased senescent CD8+ T cells in the peripheral blood mononuclear cells of Behçet’s disease patients
Tóm tắt
Behçet’s disease (BD) is a chronic inflammatory disease characterized by recurrent mucocutaneous, ocular, and skin lesions. Immunosenescence is associated with increased susceptibility to infection and chronic low grade inflammation. This study aimed to investigate the differences in the frequencies of immunosenescent cells in the peripheral blood mononuclear cells (PBMCs) of patients with BD. PBMCs were isolated from age-matched patients with active BD (n = 19), inactive BD (n = 20), disease controls (DCs, n = 15) and healthy controls (HCs, n = 15). The frequencies of senescent CD4+ T cells (CD3+ CD4+ CD27− CD28− cells), CD8+ T cells (CD3+ CD8+ CD27− CD28− cells) and B cells (CD19+ CD27− IgD− cells) were analyzed using flow cytometry. Senescence-associated β galactosidase activity was also measured in CD8+ T cells using flow cytometry with 5-dodecanoylaminofluorescein di-β-d-galactopyranoside. Frequencies of senescent CD4+ and CD19+ cells were not significantly different between the groups. The frequency of senescent CD8+ T cells was significantly higher in active BD than in DCs and HCs. C-reactive protein and erythrocyte sedimentation rate levels, which indicate disease activity, did not correlate with increased frequencies of immunosenescent cells. Steroid treatment, specific organ involvement, and HLA-B51 status did not have a significant influence on the frequencies of immunosenescent cells. Frequencies of senescence-associated β galactosidase+ CD8+ T cells were significantly higher in active BD and inactive BD compared to DCs and HCs. There was an increased frequency of senescent CD8+ T cells in the PBMCs of patients with BD.
Tài liệu tham khảo
Accardo-Palumbo A, Giardina AR, Ciccia F, Ferrante A, Principato A, Impastato R, Giardina E, Triolo G (2010) Phenotype and functional changes of Vgamma9/Vdelta2 T lymphocytes in Behcet’s disease and the effect of infliximab on Vgamma9/Vdelta2 T cell expansion, activation and cytotoxicity. Arthritis Res Ther 12:R109. https://doi.org/10.1186/ar3043
Ademokun A, Wu YC, Dunn-Walters D (2010) The ageing B cell population: composition and function. Biogerontology 11:125–137. https://doi.org/10.1007/s10522-009-9256-9
Ahn JK, Chung H, Lee DS, Yu YS, Yu HG (2005) CD8 bright CD56 + T cells are cytotoxic effectors in patients with active Behcet’s uveitis. J Immunol 175:6133–6142. https://doi.org/10.4049/jimmunol.175.9.6133
Akdeniz N, Esrefoglu M, Keleş MS, Karakuzu A, Atasoy M (2004) Serum interleukin-2, interleukin-6, tumour necrosis factor-alpha and nitric oxide levels in patients with Behcet’s disease. Ann Acad Med Singap 33:596–599
Almanzar G, Schwaiger S, Jenewein B, Keller M, Grubeck-Loebenstein B, Wurzner R, Schonitzer D (2004) IFN-gamma production by CMV-specific CD8+ T cells is high in elderly donors. Exp Gerontol 39:863–865; author reply 867–868. https://doi.org/10.1016/j.exger.2004.01.017.
Ben Ahmed M, Houman H, Miled M, Dellagi K, Louzir H (2004) Involvement of chemokines and Th1 cytokines in the pathogenesis of mucocutaneous lesions of Behcet’s disease. Arthritis Rheum 50:2291–2295. https://doi.org/10.1002/art.20334
Benagiano M, D’Elios MM, Amedei A, Azzurri A, van der Zee R, Ciervo A, Rombola G, Romagnani S, Cassone A, Del Prete G (2005) Human 60-kDa heat shock protein is a target autoantigen of T cells derived from atherosclerotic plaques. J Immunol 174:6509–6517. https://doi.org/10.4049/jimmunol.174.10.6509
Chalan P, van den Berg A, Kroesen BJ, Brouwer L, Boots A (2015) Rheumatoid arthritis, immunosenescence and the hallmarks of aging. Curr Aging Sci 8:131–146. https://doi.org/10.2174/1874609808666150727110744
Debacq-Chainiaux F, Erusalimsky JD, Campisi J, Toussaint O (2009) Protocols to detect senescence-associated beta-galactosidase (SA-betagal) activity, a biomarker of senescent cells in culture and in vivo. Nat Protoc 4:1798–1806. https://doi.org/10.1038/nprot.2009.191
Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O, Peacocke M, Campisi J (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA 92:9363–9367. https://doi.org/10.1073/pnas.92.20.9363
Direskeneli H, Saruhan-Direskeneli G (2003) The role of heat shock proteins in Behcet’s disease. Clin Exp Rheumatol 21(4 Suppl 30):S44-S48
Ekinci NS, Alpsoy E, Karakas AA, Yilmaz SB, Yegin O (2010) IL-17A has an important role in the acute attacks of Behcet’s disease. J Invest Dermatol 130:2136–2138. https://doi.org/10.1038/jid.2010.114
Galeone M, Colucci R, D’Erme AM, Moretti S, Lotti T (2012) Potential infectious etiology of Behcet’s disease. Patholog Res Int 2012:595380. https://doi.org/10.1155/2012/595380
Goronzy JJ, Lee WW, Weyand CM (2007) Aging and T-cell diversity. Exp Gerontol 42:400–406. https://doi.org/10.1016/j.exger.2006.11.016
Gu Z, Cao X, Jiang J, Li L, Da Z, Liu H, Cheng C (2012) Upregulation of p16INK4A promotes cellular senescence of bone marrow-derived mesenchymal stem cells from systemic lupus erythematosus patients. Cell Signal 24:2307–2314. https://doi.org/10.1016/j.cellsig.2012.07.012
Guenane H, Hartani D, Chachoua L, Lahlou-Boukoffa OS, Mazari F, Touil-Boukoffa C (2006) Production of Th1/Th2 cytokines and nitric oxide in Behçet’s uveitis and idiopathic uveitis. J Fr Ophtalmol 29:146–152
Hatemi G, Silman A, Bang D, Bodaghi B, Chamberlain AM, Gul A, Houman MH, Kotter I, Olivieri I, Salvarani C, Sfikakis PP, Siva A, Stanford MR, Stubiger N, Yurdakul S, Yazici H (2008) EULAR recommendations for the management of Behcet disease. Ann Rheum Dis 67:1656–1662. https://doi.org/10.1136/ard.2007.080432
Imirzalioglu N, Dursun A, Tastan B, Soysal Y, Yakicier MC (2005) MEFV gene is a probable susceptibility gene for Behcet’s disease. Scand J Rheumatol 34:56–58. https://doi.org/10.1080/03009740510017931
International Study Group for Behçet’s Disease (1990) Criteria for diagnosis of Behcet’s disease. Lancet 335:1078–1080. https://doi.org/10.1016/0140-6736(90)92643-V
Irschick EU, Philipp S, Shahram F, Schirmer M, Sedigh M, Ziaee N, Gassner C, Schennach H, Meyer M, Larcher C, Herold M, Schoenitzer D, Fuchs D, Schoenbauer M, Maass M, Huemer HP, Davatchi F (2011) Investigation of bacterial and viral agents and immune status in Behcet’s disease patients from Iran. Int J Rheum Dis 14:298–310. https://doi.org/10.1111/j.1756-185X.2011.01601.x
Keller M, Spanou Z, Schaerli P, Britschgi M, Yawalkar N, Seitz M, Villiger PM, Pichler WJ (2005) T cell-regulated neutrophilic inflammation in autoinflammatory diseases. J Immunol 175:7678–7686. https://doi.org/10.4049/jimmunol.175.11.7678
Lang A, Brien JD, Nikolich-Zugich J (2009) Inflation and long-term maintenance of CD8 T cells responding to a latent herpesvirus depend upon establishment of latency and presence of viral antigens. J Immunol 183:8077–8087. https://doi.org/10.4049/jimmunol.0801117
Lee S, Bang D, Cho YH, Lee ES, Sohn S (1996) Polymerase chain reaction reveals herpes simplex virus DNA in saliva of patients with Behcet’s disease. Arch Dermatol Res 288:179–183. https://doi.org/10.1007/BF02505221
Lehner T, Lavery E, Smith R, van der Zee R, Mizushima Y, Shinnick T (1991) Association between the 65-kilodalton heat shock protein, Streptococcus sanguis, and the corresponding antibodies in Behcet’s syndrome. Infect Immun 59:1434–1441
Liang L, Tan X, Zhou Q, Zhu Y, Tian Y, Yu H, Kijlstra A, Yang P (2013) IL-1beta triggered by peptidoglycan and lipopolysaccharide through TLR2/4 and ROS-NLRP3 inflammasome-dependent pathways is involved in ocular Behcet’s disease. Invest Ophthalmol Vis Sci 54:402–414. https://doi.org/10.1167/iovs.12-11047
Lu Y, Ye P, Chen SL, Tan EM, Chan EK (2005) Identification of kinectin as a novel Behçet’s disease autoantigen. Arthritis Res Ther 7:R1133–R1139. https://doi.org/10.1186/ar1798
Martin JM, Mateo E, Monteagudo C, Jorda E (2010) Severe flare of Behcet’s disease with intense mucucutaneous manifestations. Reumatol Clin 6:303–305. https://doi.org/10.1016/j.reuma.2010.05.001
Mochizuki M, Morita E, Yamamoto S, Yamana S (1997) Characteristics of T cell lines established from skin lesions of Behcet’s disease. J Dermatol Sci 15:9–13. https://doi.org/10.1016/S0923-1811(96)00588-9
Na SY, Park MJ, Park S, Lee ES (2013) Up-regulation of Th17 and related cytokines in Behcet’s disease corresponding to disease activity. Clin Exp Rheumatol 31(3 Suppl 77):S32-S40
Nalbant S, Sahan B, Durna M, Ersanli D, Kaplan M, Karabudak O, Unal M (2008) Cytokine profile in Behçet uveitis. Bratisl Lek Listy 109:551–554
Pawelec G (1999) Immunosenescence: impact in the young as well as the old? Mech Ageing Dev 108:1–7. https://doi.org/10.1016/S0047-6374(99)00010-X
Pawelec G (2014) Immunosenescence: role of cytomegalovirus. Exp Gerontol 54:1–5. https://doi.org/10.1016/j.exger.2013.11.010
Rossol M, Kraus S, Pierer M, Baerwald C, Wagner U (2012) The CD14(bright) CD16+ monocyte subset is expanded in rheumatoid arthritis and promotes expansion of the Th17 cell population. Arthritis Rheum 64:671–677. https://doi.org/10.1002/art.33418
Sakane T, Takeno M, Suzuki N, Inaba G (1999) Behcet’s disease. N Engl J Med 341:1284–1291. https://doi.org/10.1056/nejm199910213411707
Shao L, Fujii H, Colmegna I, Oishi H, Goronzy JJ, Weyand CM (2009) Deficiency of the DNA repair enzyme ATM in rheumatoid arthritis. J Exp Med 206:1435–1449. https://doi.org/10.1084/jem.20082251
Shao L, Goronzy JJ, Weyand CM (2010) DNA-dependent protein kinase catalytic subunit mediates T-cell loss in rheumatoid arthritis. EMBO Mol Med 2:415–427. https://doi.org/10.1002/emmm.201000096
Studd M, McCance DJ, Lehner T (1991) Detection of HSV-1 DNA in patients with Behcet’s syndrome and in patients with recurrent oral ulcers by the polymerase chain reaction. J Med Microbiol 34:39–43. https://doi.org/10.1099/00222615-34-1-39
Suzuki Kurokawa M, Suzuki N (2004) Behcet’s disease. Clin Exp Med 4:10–20. https://doi.org/10.1007/s10238-004-0033-4
Šahmatova L, Sügis E, Šunina M, Hermann H, Prans E, Pihlap M, Abram K, Rebane A, Peterson H, Peterson P, Kingo K, Kisand K (2017) Signs of innate immune activation and premature immunosenescence in psoriasis patients. Sci Rep 7:7553. https://doi.org/10.1038/s41598-017-07975-2
Takeuchi M, Kastner DL, Remmers EF (2015) The immunogenetics of Behcet’s disease: a comprehensive review. J Autoimmun 64:137–148. https://doi.org/10.1016/j.jaut.2015.08.013
Targonski PV, Jacobson RM, Poland GA (2007) Immunosenescence: role and measurement in influenza vaccine response among the elderly. Vaccine 25:3066–3069. https://doi.org/10.1016/j.vaccine.2007.01.025
Weiskopf D, Weinberger B, Grubeck-Loebenstein B (2009) The aging of the immune system. Transpl Int 22:1041–1050. https://doi.org/10.1111/j.1432-2277.2009.00927.x
Yuksel S, Eren E, Hatemi G, Sahillioglu AC, Gultekin Y, Demiroz D, Akdis C, Fresko I, Ozoren N (2014) Novel NLRP3/cryopyrin mutations and pro-inflammatory cytokine profiles in Behcet’s syndrome patients. Int Immunol 26:71–81. https://doi.org/10.1093/intimm/dxt046
Zhang X, Meng X, Chen Y, Leng SX, Zhang H (2017) The biology of aging and cancer: frailty, inflammation, and immunity. Cancer J 23:201–205. https://doi.org/10.1097/PPO.0000000000000270