Abstract
Several studies have demonstrated T cell alteration and some features of immunosenescence in thalassemia major. Repeated alloimmunization converts naïve T-cells to memory cells and iron overload causes oxidative stress accelerating immune aging. To determine whether the alteration of T-cell cytokine is matched with early immune aging, the quantity of cytokine expressing T cells and their correlation to some immune aging markers were investigated. The proportion of IL2- and IFNγ expressing CD4+ and CD8+ T-cells was measured in 27 hepatitis B, C and HIV negative B-thalassemia patients and a control group aged 10–30 years, following stimulation for 6 h with streptococcus enterotoxin B and intracellular cytokine staining. This proportion then were analyzed versus the percentage of the T-cells expressing each phenotyping marker, CD27, CD28, CD57 and CCR7. CD4+ and CD8+ positive T cells expressing IL-2 were significantly lower in β-thalassemia major compared to matched controls, but not T cells expressing IFNγ. No significant difference was observed between splenectomized and non-splenectomized patients in cytokine expressing T cells. A negative correlation was noted between the percentage of T cells expressing IFNγ and T-cells expressing CD-27, but not other markers. Lower T cells expressing IL-2 may reveal the decline of naïve and central memory T cells and is likely to be a feature of early immune aging. Decreased antigenic stimulation and iron overload may help to prevent this phenomenon.
Similar content being viewed by others
References
Rahimi Z, Muniz A, Akramipour R, Tofieghzadeh F, Mozafari H, Vaisi-Raygani A et al (2009) Haplotype analysis of beta thalassemia patients in Western Iran. Blood Cells Mol Dis 42(2):140–143
Kassab-Chekir A, Laradi S, Ferchichi S, Haj Khelil A, Feki M, Amri F et al (2003) Oxidant, antioxidant status and metabolic data in patients with beta-thalassemia. Clin Chim Acta Int J Clin Chem 338(1–2):79–86
Rachmilewitz EA, Weizer-Stern O, Adamsky K, Amariglio N, Rechavi G, Breda L et al (2005) Role of iron in inducing oxidative stress in thalassemia: can it be prevented by inhibition of absorption and by antioxidants? Ann N Y Acad Sci 1054:118–123
Schrier SL, Centis F, Verneris M, Ma L, Angelucci E (2003) The role of oxidant injury in the pathophysiology of human thalassemias. Redox Rep Commun Free Radic Res 8(5):241–245
Farmakis D, Giakoumis A, Polymeropoulos E, Aessopos A (2003) Pathogenetic aspects of immune deficiency associated with beta-thalassemia. Med Sci Monit 9(1):RA19–RA22
Gharagozloo M, Karimi M, Amirghofran Z (2009) Double-faced cell-mediated immunity in β-thalassemia major: stimulated phenotype versus suppressed activity. Ann Hematol 88(1):21–27
Roshdy MN, Harfoush RA, Hamed NA, Morsi MG (2013) Quantitative estimation of interferon-gamma levels among Egyptian polytransfused haematology cases. Eastern Mediterranean health journal = La revue de sante de la Mediterranee orientale = al-Majallah al-sihhiyah li-sharq al-mutawassit 19(5):490–494
Poland GA, Ovsyannikova IG, Kennedy RB, Lambert ND, Kirkland JL (2014) A systems biology approach to the effect of aging, immunosenescence and vaccine response. Curr Opin Immunol 29:62–68
Bernstein E, Kaye D, Abrutyn E, Gross P, Dorfman M, Murasko DM (1999) Immune response to influenza vaccination in a large healthy elderly population. Vaccine 17(1):82–94
Karrer U, Sierro S, Wagner M, Oxenius A, Hengel H, Koszinowski UH et al (2003) Memory inflation: continuous accumulation of antiviral CD8 + T cells over time. J Immunol (Baltimore, Md: 1950) 170(4):2022–2029
Voskou S, Aslan M, Fanis P, Phylactides M, Kleanthous M (2015) Oxidative stress in beta-thalassaemia and sickle cell disease. Redox Biol 6:226–239
Pawelec G, Akbar A, Caruso C, Solana R, Grubeck-Loebenstein B, Wikby A (2005) Human immunosenescence: is it infectious? Immunol Rev 205(1):257–268
Sari TT, Gatot D, Akib AA, Bardosono S, Hadinegoro SR, Harahap AR et al (2014) Immune response of thalassemia major patients in Indonesia with and without splenectomy. Acta Med Indones 46(3):217–225
Velasquez SY, Garcia LF, Opelz G, Alvarez CM, Susal C (2013) Release of soluble CD30 after allogeneic stimulation is mediated by memory T cells and regulated by IFN-gamma and IL-2. Transplantation 96(2):154–161
Provinciali M, Moresi R, Donnini A, Lisa RM (2009) Reference values for CD4+ and CD8+ T lymphocytes with naive or memory phenotype and their association with mortality in the elderly. Gerontology 55(3):314–321
Li G, Ju J, Weyand CM, Goronzy JJ (2015) Age-associated failure to adjust type I IFN receptor signaling thresholds after T cell activation. J Immunol (Baltimore, Md: 1950) 195(3):865–874
Pourgheysari B, Bruton R, Parry H, Billingham L, Fegan C, Murray J et al (2010) The number of cytomegalovirus-specific CD4 + T cells is markedly expanded in patients with B-cell chronic lymphocytic leukemia and determines the total CD4 + T-cell repertoire. Blood 116(16):2968–2974
Jang TY, Lin PC, Huang CI, Liao YM, Yeh ML, Zeng YS et al (2017) Seroprevalence and clinical characteristics of viral hepatitis in transfusion-dependent thalassemia and hemophilia patients. PLoS ONE 12(6):e0178883
Mahzounieh M, Ghorani M, Karimi A, Pourgheysari B, Nikoozad R (2015) Prevalence of human T-lymphotropic virus types I and II in patients with hematological disorders in Isfahan, Iran. Jundishapur J Microbiol 8(6):e17201
Al-Awadhi AM, Alfadhli SM, Al-Khaldi D, Borhama M, Borusly M (2010) Investigation of the distribution of lymphocyte subsets and zinc levels in multitransfused beta-thalassemia major patients. Int J Lab Hematol 32(2):191–196
Gharagozloo M, Bagherpour B, Tahanian M, Oreizy F, Amirghofran Z, Sadeghi HM et al (2009) Premature senescence of T lymphocytes from patients with beta-thalassemia major. Immunol Lett 122(1):84–88
Pourgheysari B, Karimi L, Beshkar P (2016) Alteration of T cell subtypes in beta-thalassaemia major: impact of ferritin level. JCDR 10(2):Dc8–Dc14
Kallies A (2008) Distinct regulation of effector and memory T-cell differentiation. Immunol Cell Biol 86(4):325–332
Bao W, Zhong H, Li X, Lee MT, Schwartz J, Sheth S et al (2011) Immune regulation in chronically transfused allo-antibody responder and nonresponder patients with sickle cell disease and beta-thalassemia major. Am J Hematol 86(12):1001–1006
Bozdogan G, Erdem E, Demirel GY, Yildirmak Y (2010) The role of Treg cells and FoxP3 expression in immunity of beta-thalassemia major AND beta-thalassemia trait patients. Pediatr Hematol Oncol 27(7):534–545
Trzonkowski P, Szmit E, Mysliwska J, Mysliwski A (2006) CD4 + CD25 + T regulatory cells inhibit cytotoxic activity of CTL and NK cells in humans-impact of immunosenescence (Orlando, Fla). Clin Immunol 119(3):307–316
Al-Ofairi BA, Barakat AB, Ghanim Hel D, Shehata IH, El-Sayed MH (2011) A study of innate and adaptive immune responses in beta-thalassemic patients with chronic hepatitis C virus infection. Egypt J Immunol 18(1):61–76
Butthep P, Wisedpanichkij R, Jindadamrongwech S, Fucharoen S (2015) Elevated erythropoietin and cytokines levels are related to impaired reticulocyte maturation in thalassemic patients. Blood Cells Mol Dis 54(2):170–176
Pourgheysari B, Khan N, Best D, Bruton R, Nayak L, Moss PA (2007) The cytomegalovirus-specific CD4 + T-cell response expands with age and markedly alters the CD4 + T-cell repertoire. J Virol 81(14):7759–7765
Mendez-Lagares G, Diaz L, Correa-Rocha R, Leon Leal JA, Ferrando-Martinez S, Ruiz-Mateos E et al (2013) Specific patterns of CD4-associated immunosenescence in vertically HIV-infected subjects. Clin Microbiol Infect 19(6):558–565
Albareda MC, Olivera GC, De Rissio AM, Postan M (2010) Assessment of CD8(+) T cell differentiation in Trypanosoma cruzi-infected children. Am J Trop Med Hyg 82(5):861–864
Kern F, Khatamzas E, Surel I, Frommel C, Reinke P, Waldrop SL et al (1999) Distribution of human CMV-specific memory T cells among the CD8pos. subsets defined by CD57, CD27, and CD45 isoforms. Eur J Immunol 29(9):2908–2915
Acknowledgements
This study was supported by the Deputy of Research and Technology of the Shahrekord University of Medical Sciences with the Grant No. 916 obtained by first author.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declared no competing interests.
Ethics Committee
Ethical Approval for the study was obtained from the Shahrekord University of Medical Sciences Ethics Committee. Informed consent was obtained from all individual participants included in the study.
Rights and permissions
About this article
Cite this article
Pourgheysari, B., Karimi, L., Bagheri, R. et al. Low IL-2 Expressing T Cells in Thalassemia Major Patients: Is It Immune Aging. Indian J Hematol Blood Transfus 34, 653–661 (2018). https://doi.org/10.1007/s12288-018-0939-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12288-018-0939-8