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The shortening telomere length of T lymphocytes maybe associated with hyper‑function in servere aplastic anemia

  • Authors:
    • Chaomeng Wang
    • Tian Zhang
    • Yihao Wang
    • Yang Li
    • Chunyan Liu
    • Hui Liu
    • Lijuan Li
    • Kai Ding
    • Ting Wang
    • Honglei Wang
    • Zonghong Shao
    • Rong Fu
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1015-1021
    |
    Published online on: November 8, 2017
       https://doi.org/10.3892/mmr.2017.8014
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Abstract

Severe aplastic anemia (SAA) is a primary disorder of severe bone marrow failure characterizing with extreme pancytopenia and a profound diminution of bone marrow progenitor cells, which is associated with T cell hyper‑function. Abnormal telomere shortening of bone marrow mononuclear cell has been reported in AA, which may lead to genomic instability, and result in cell senescence or apoptosis. Notably, certain studies identfieid that lymphocytes of shortening telomere length have undergone apoptosis escape in autoimmune diseases. In order to investigate the association between telomere lengths and function of T lymphocytes in SAA, the relative telomere lengths (RTLs) of different subtypes of T lymphocytes were investigated by flow‑fluorescent in situ hybridization in 30 patients with SAA and 25 healthy controls. Then the levels of expression of cluster of differentiation 28 (CD28), CD158 and CD70 were measured, which represent the function of T lymphocytes. The apoptosis rate and the cell cycle progression of CD8+T lymphocytes, and the level of secretion interferon‑γ and tumor necrosis factor‑α were also measured. Finally, the correlation between telomere length and these functional events of CD8+T lymphocytes was analyzed in patients with SAA. The results showed that RTLs of CD8+T lymphocytes in SAA were significantly shorter compared with those in controls. Furthermore, in patients with SAA, CD8+T lymphocytes are associated with T cell hyper‑function, which is related to the RTL. Thus, the shorter RTLs of CD8+T lymphocytes in SAA may be associated with hyper‑function of these cells, which contribute to the pathogenesis of SAA.
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View References

1 

Bacigalupo A: Aplastic anemia: Pathogenesis and treatment. Hematology Am Soc Hematol Educ Program. 23–28. 2007.PubMed/NCBI

2 

Marsh JC, Ball SE, Cavenagh J, Darbyshire P, Dokal I, Gordon-Smith EC, Keidan J, Laurie A, Martin A, Mercieca J, et al: Guidelines for the diagnosis and management of aplastic anaemia. Br J Haematol. 147:43–70. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Young NS, Calado RT and Scheinberg P: Current concepts in the pathophysiology and treatment of aplastic anemia. Blood. 108:2509–2519. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Zoumbos NC, Gascon P, Djeu JY and Young NS: Interferon is a mediator of hematopoietic suppression in aplastic anemia in vitro and possibly in vivo. Proc Natl Acad Sci USA. 82:188–192. 1985. View Article : Google Scholar : PubMed/NCBI

5 

Liu X, Fu R, Wang HQ, Liu CY, Ruan EB, Qu W, Liang Y, Wang GJ, Wang XM, Liu H, et al: Research of regulative factors on CD8(+)HLA-DR(+) effector T cells in severe aplastic anemia. Zhonghua Yi Xue Za Zhi. 92:1665–1668. 2012.(In Chinese). PubMed/NCBI

6 

Solomou EE, Rezvani K, Mielke S, Malide D, Keyvanfar K, Visconte V, Kajigaya S, Barrett AJ and Young NS: Deficient CD4+CD25+FOXP3+ T regulatory cells in acquired aplastic anemia. Blood. 110:1603–1606. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Longhese MP: DNA damage response at functional and dysfunctional telomeres. Genes Dev. 22:125–140. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A, Moss H and de Lange T: Mammalian telomeres end in a large duplex loop. Cell. 97:503–514. 1999. View Article : Google Scholar : PubMed/NCBI

9 

de Lange T: Shelterin: The protein complex that shapes and safeguards human telomeres. Genes Dev. 19:2100–2110. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Hayflick L: The limited in vitro lifetime of human diploid cell strains. Exp Cell Res. 37:614–636. 1965. View Article : Google Scholar : PubMed/NCBI

11 

Wang T, Mei SC, Fu R, Wang HQ and Shao ZH: Expression of Shelterin component POT1 is associated with decreased telomere length and immunity condition in humans with severe aplastic anemia. J Immunol Res. 2014:4395302014. View Article : Google Scholar : PubMed/NCBI

12 

Ma XC, Liu CY, Sun XJ, He JJ, Wan SG and Sun WL: Genetic characteristics of human acute lymphoblastic leukemia cell line Molt-4. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 22:280–284. 2014.(In Chinese). PubMed/NCBI

13 

Jing Yan, Kang Min, Liu Jin, Li Jingyu and Tang Anzhou: Mechanism of apoptosis of nasopharyngeal carcinoma cells induced by polysaccharides extracts from Hedyotic diffusa. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 29:641–644. 2015.(In Chinese). PubMed/NCBI

14 

Calado RT and Dumitriu B: Telomere dynamics in mice and humans. Semin Hematol. 50:165–174. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Son NH, Murray S, Yanovski J, Hodes RJ and Weng N: Lineage-specific telomere shortening and unaltered capacity for telomerase expression in human T and B lymphocytes with age. J Immunol. 165:1191–1196. 2000. View Article : Google Scholar : PubMed/NCBI

16 

Goronzy JJ, Fujii H and Weyand CM: Telomeres, immune aging and autoimmunity. Exp Gerontol. 41:246–251. 2006. View Article : Google Scholar : PubMed/NCBI

17 

Klapper W, Moosig F, Sotnikova A, Qian W, Schröder JO and Parwaresch R: Telomerase activity in B and T lymphocytes of patients with systemic lupus erythematosus. Ann Rheum Dis. 63:1681–1683. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Blasco MA: Immunosenescence phenotypes in the telomerase knockout mouse. Springer Semin Immunopathol. 24:75–85. 2002. View Article : Google Scholar : PubMed/NCBI

19 

Kipling D: Telomeres, replicative senescence and human ageing. Maturitas. 38:25–38. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Klapper W, Parwaresch R and Krupp G: Telomere biology in human aging and aging syndromes. Mech Ageing Dev. 122:695–712. 2001. View Article : Google Scholar : PubMed/NCBI

21 

Scheinberg P, Cooper JN, Sloand EM, Wu CO, Calado RT and Young NS: Association of telomere length of peripheral blood leukocytes with hematopoietic relapse, malignant transformation, and survival in severe aplastic anemia. JAMA. 304:1358–1364. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Calado RT, Cooper JN, Padilla-Nash HM, Sloand EM, Wu CO, Scheinberg P, Ried T and Young NS: Short telomeres result in chromosomal instability in hematopoietic cells and precede malignant evolution in human aplastic anemia. Leukemia. 26:700–707. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Wang T, Fu R, Wang HQ, Qu W, Ruan EB, Wang GJ, Liu H, Wu YH, Wang XM, Song J, et al: Telomere length and gene expression of shelterin in CD3(+) T cell of severe aplastic anemia patients. Zhonghua Yi Xue Za Zhi. 93:1533–1536. 2013.(In Chinese). PubMed/NCBI

24 

Brümmendorf TH, Maciejewski JP, Mak J, Young NS and Lansdorp PM: Telomere length in leukocyte subpopulations of patients with aplastic anemia. Blood. 97:895–900. 2001. View Article : Google Scholar : PubMed/NCBI

25 

Fagnoni FF, Vescovini R, Mazzola M, Bologna G, Nigro E, Lavagetto G, Franceschi C, Passeri M and Sansoni P: Expansion of cytotoxic CD8+CD28− T cells in healthy ageing people, including centenarians. Immunology. 88:501–507. 1996. View Article : Google Scholar : PubMed/NCBI

26 

Li D, Gál I, Vermes C, Alegre ML, Chong AS, Chen L, Shao Q, Adarichev V, Xu X, Koreny T, et al: Cutting edge: Cbl-b: One of the key molecules tuning CD28- and CTLA-4-mediated T cell costimulation. J Immunol. 173:7135–7139. 2004. View Article : Google Scholar : PubMed/NCBI

27 

Riley JL and June CH: The CD28 family: A T-cell rheostat for therapeutic control of T-cell activation. Blood. 105:13–21. 2005. View Article : Google Scholar : PubMed/NCBI

28 

Weng NP, Akbar AN and Goronzy J: CD28(−) T cells: Their role in the age-associated decline of immune function. Trends Immunol. 30:306–312. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Borst J, Hendriks J and Xiao Y: CD27 and CD70 in T cell and B cell activation. Curr Opin Immunol. 17:275–281. 2005. View Article : Google Scholar : PubMed/NCBI

30 

Coquet JM, Middendorp S, van der Horst G, Kind J, Veraar EA, Xiao Y, Jacobs H and Borst J: The CD27 and CD70 costimulatory pathway inhibits effector function of T helper 17 cells and attenuates associated autoimmunity. Immunity. 38:53–65. 2013. View Article : Google Scholar : PubMed/NCBI

31 

Nazari M, Mahmoudi M, Rahmani F, Akhlaghi M, Beigy M, Azarian M, Shamsian E, Akhtari M and Mansouri R: Association of killer cell immunoglobulin-like receptor genes in iranian patients with rheumatoid arthritis. PLoS One. 10:e1437572015. View Article : Google Scholar

32 

Schirmer M, Goldberger C, Würzner R, Duftner C, Pfeiffer KP, Clausen J, Neumayr G and Falkenbach A: Circulating cytotoxic CD8(+) CD28(−) T cells in ankylosing spondylitis. Arthritis Res. 4:71–76. 2002. View Article : Google Scholar : PubMed/NCBI

33 

Sun Z, Yi L, Tao H, Huang J, Jin Z, Xiao Y, Feng C and Sun J: Enhancement of soluble CD28 levels in the serum of Graves' disease. Cent Eur J Immunol. 39:216–222. 2014. View Article : Google Scholar : PubMed/NCBI

34 

Young NS, Bacigalupo A and Marsh JC: Aplastic anemia: Pathophysiology and treatment. Biol Blood Marrow Transplant. 16 Suppl 1:S119–S125. 2010. View Article : Google Scholar : PubMed/NCBI

35 

Georgin-Lavialle S, Aouba A, Mouthon L, Londono-Vallejo JA, Lepelletier Y, Gabet AS and Hermine O: The telomere/telomerase system in autoimmune and systemic immune-mediated diseases. Autoimmun Rev. 9:646–651. 2010. View Article : Google Scholar : PubMed/NCBI

36 

Jeanclos E, Krolewski A, Skurnick J, Kimura M, Aviv H, Warram JH and Aviv A: Shortened telomere length in white blood cells of patients with IDDM. Diabetes. 47:482–486. 1998. View Article : Google Scholar : PubMed/NCBI

37 

Kurosaka D, Yasuda J, Yoshida K, Yoneda A, Yasuda C, Kingetsu I, Toyokawa Y, Yokoyama T, Saito S and Yamada A: Abnormal telomerase activity and telomere length in T and B cells from patients with systemic lupus erythematosus. J Rheumatol. 33:1102–1107. 2006.PubMed/NCBI

38 

Wu CH, Hsieh SC, Li KJ, Lu MC and Yu C: Premature telomere shortening in polymorphonuclear neutrophils from patients with systemic lupus erythematosus is related to the lupus disease activity. Lupus. 16:265–272. 2007. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wang C, Zhang T, Wang Y, Li Y, Liu C, Liu H, Li L, Ding K, Wang T, Wang H, Wang H, et al: The shortening telomere length of T lymphocytes maybe associated with hyper‑function in servere aplastic anemia. Mol Med Rep 17: 1015-1021, 2018.
APA
Wang, C., Zhang, T., Wang, Y., Li, Y., Liu, C., Liu, H. ... Fu, R. (2018). The shortening telomere length of T lymphocytes maybe associated with hyper‑function in servere aplastic anemia. Molecular Medicine Reports, 17, 1015-1021. https://doi.org/10.3892/mmr.2017.8014
MLA
Wang, C., Zhang, T., Wang, Y., Li, Y., Liu, C., Liu, H., Li, L., Ding, K., Wang, T., Wang, H., Shao, Z., Fu, R."The shortening telomere length of T lymphocytes maybe associated with hyper‑function in servere aplastic anemia". Molecular Medicine Reports 17.1 (2018): 1015-1021.
Chicago
Wang, C., Zhang, T., Wang, Y., Li, Y., Liu, C., Liu, H., Li, L., Ding, K., Wang, T., Wang, H., Shao, Z., Fu, R."The shortening telomere length of T lymphocytes maybe associated with hyper‑function in servere aplastic anemia". Molecular Medicine Reports 17, no. 1 (2018): 1015-1021. https://doi.org/10.3892/mmr.2017.8014
Copy and paste a formatted citation
x
Spandidos Publications style
Wang C, Zhang T, Wang Y, Li Y, Liu C, Liu H, Li L, Ding K, Wang T, Wang H, Wang H, et al: The shortening telomere length of T lymphocytes maybe associated with hyper‑function in servere aplastic anemia. Mol Med Rep 17: 1015-1021, 2018.
APA
Wang, C., Zhang, T., Wang, Y., Li, Y., Liu, C., Liu, H. ... Fu, R. (2018). The shortening telomere length of T lymphocytes maybe associated with hyper‑function in servere aplastic anemia. Molecular Medicine Reports, 17, 1015-1021. https://doi.org/10.3892/mmr.2017.8014
MLA
Wang, C., Zhang, T., Wang, Y., Li, Y., Liu, C., Liu, H., Li, L., Ding, K., Wang, T., Wang, H., Shao, Z., Fu, R."The shortening telomere length of T lymphocytes maybe associated with hyper‑function in servere aplastic anemia". Molecular Medicine Reports 17.1 (2018): 1015-1021.
Chicago
Wang, C., Zhang, T., Wang, Y., Li, Y., Liu, C., Liu, H., Li, L., Ding, K., Wang, T., Wang, H., Shao, Z., Fu, R."The shortening telomere length of T lymphocytes maybe associated with hyper‑function in servere aplastic anemia". Molecular Medicine Reports 17, no. 1 (2018): 1015-1021. https://doi.org/10.3892/mmr.2017.8014
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