Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2016, vol. 25, nr 4, July-August, p. 665–671

doi: 10.17219/acem/60714

Publication type: original article

Language: English

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Abnormal Distribution of Gamma-Delta T Lymphocytes and Their Subsets in Type 1 Diabetes

Agnieszka Zubkiewicz-Kucharska1,A,B,C,D,E,F, Anna Noczyńska1,A,C,E,F, Lidia Usnarska-Zubkiewicz,A,C,E,F

1

Abstract

Background. It was assumed that T γδ lymphocytes (T γδ) are involved in the autoimmune destruction of beta cells, presumably as regulatory cells.
Objectives. The aim of this paper was to investigate T γδ cells mean percentage (%) in peripheral blood in patients with type 1 diabetes (T1DM) at the time of diagnosis and after twelve months of observation.
Material and Methods. A total of 41 patients (21 boys, 51.2%) with new-onset T1DM were included. Exclusion criteria were: Other autoimmune disease, neoplasm, and inflammation. The control group comprised of 14 healthy (7 boys, 50.0%), normostenic children, with normal glucose metabolism and negative history of autoimmune disease and/or diabetes in family.
Results. The mean T γδ % in patients with new-onset T1DM (8.03 ± 3.80) and after 12-months of follow-up (6.13 ± 2.15) was lower than in controls (11.23 ± 6.79), p = 0.042 and p = 0.016, respectively. A depletion of those cells after one year was observed (p = 0.067). Gender did not affect the level of T γδ and subsets. No association between T γδ and age neither in T1DM nor controls was observed.
Conclusion. Our results support the hypotheses that T γδ play a role in T1DM pathogenesis. If so, the decrease of those lymphocytes makes the probands more vulnerable to autoaggression. We report here for the first time the further depletion of T γδ after one year of insulin treatment, which may be due to the exacerbation of beta cell destruction in the course of insulitis.

Key words

immune tolerance, type 1 diabetes, T γδ lymphocytes

References (29)

  1. Atkinson MA, Eisenbarth GS: Type 1 diabetes: New perspectives on disease pathogenesis and treatment. Lancet 2001, 358, 221–229.
  2. Li CR, Baaten BJ, Bradley LM: Harnessing memory adaptive regulatory T cells to control autoimmunity in type 1 diabetes. J Mol Cell Biol 2012, 4, 38–47.
  3. Champagne E: γδ T cell receptor ligands and modes of antigen recognition. Arch Immunol Ther Exp (Warsz) 2011, 59, 117–137.
  4. Caccamo N, Dieli F, Wesch D, Jomaa H, Eberl M: Sex-specific phenotypical and functional differences in peripheral human Vγ9/Vδ2 T cells. J Leukoc Biol 2006, 79, 663–666.
  5. Lang FP, Pollock BH, Riley WJ, Maclaren NK, Barrett DJ: The temporal association between gamma delta T cells and the natural history of insulin-dependent diabetes. J Autoimmun 1993, 6, 107–119.
  6. Hänninen A, Harrison LC: γδ T cels as mediators of mucosal tolerance: the autoimmune diabetes model. Immunol Rev 2000, 173, 109–119.
  7. Markle JG, Mortin-Toth S, Wong AS, Geng L, Hayday A, Danska JS: γδ T cells are essential effectors of type 1 diabetes in the nonobese diabetic mouse model. J Immunol 2013, 190, 5392–5401.
  8. Bossowski A, Urban M, Stasiak-Barmuta A: Analysis of circulating T gamma/delta lymphocytes and CD16/56 cell populations in children and adolescents with Graves’ disease. Pediatr Res 2003, 54, 425–429.
  9. Bhagat G, Naiyer AJ, Shah JG, Harper J, Jabri B, Wang TC, Green PH, Manavalan JS: Small intestinal CD8+TCR gamma delta+ NKG2A+ intraepithelial lymphocytes have attributes of regulatory cells in patients with celiac disease. J Clin Invest 2008, 118, 281–293.
  10. Zubkiewicz-Kucharska A, Noczyńska A, Usnarska-Zubkiewicz L: Rola limfocytów T γδ w patogenezie cukrzycy typu 1. Endokrynol Pediatr 2014, 13, 31–39.
  11. Ziegler HK: The role of gamma/delta T cells in immunity to infection and regulation of inflammation. Immunol Res 2004, 29, 293–302.
  12. Robak E, Błoński JZ, Bartkowiak J, Niewiadomska H, Sysa-Jędrzejowska A, Robak T: Circulating TCR γδ cells in the patients with systemic lupus erythematosus. Mediators Inflamm 1999, 8, 305–312.
  13. Borst J, Vroom TM, Bos JD, van Dongen JJM: Tissue distribution and repetoire selection of human γδ cells: Comparison with the murine system. Curret Topics MicrobiolImmunol 1991, 173, 41–46.
  14. Lafont V, Loisel S, Liautard J, Dudal S, Sable-Teychene M, Liautard JP, Favero J: Specific signaling pathways triggered by IL-2 in human V gamma 9 V delta 2 T cells: An amalgamation of NK and alpha beta cell signaling. J Immunol 2003, 171, 5225–5232.
  15. Groh V, Porcelli S, Fabbi M, Lanier LL, Picker LJ, Andreson T, Warnke RA, Bhan AK, Strominger JL, Brenner MB: Human lymphocytes bearing T cell receptor γ/δ are phenotypically diverse and evenly distributed throught the lymphoid system. J Exp Med 1989, 169, 1277–1294.
  16. Hviid L, Akanmori BD, Loizon S, Kurtzhals JA, Ricke CH, Lim A, Koram KA, Nkrumah FK, MercereauPuijalon O, Behr C: High frequency of circulating gamma delta T cells with dominance of the v(delta)1 subset in a healthy population. Int Immunol 2000, 12, 797–805.
  17. Szczepańska M, Bulsa J, Sędek Ł, Muszewska E, Morawiec-Knysak A, Matyl A, Sonsala A, Mazur B, Karpe J, Szczepański T: Subpopulacje limfocytów T i komórek NK we krwi obwodowej u zdrowych dzieci w wieku 3–19 lat. Pediatr Pol 2011, 86, 123–132.
  18. Ernerudh J, Ludvigsson J, Berlin G, Samuelsson U: Effect of photopheresis on lymphocyte population in children with newly diagnosed type 1 diabetes. Clin Diagn Lab Immunol 2004, 11, 856–861.
  19. Han G, Wang R, Chen G, Wang J, Xu R, Wang L, Feng J, Li X, Guo R, Fu L, Shen B, Li Y: Interleukin-17 producing gammadelta+ T cells protect NOD mice from type 1 diabetes through a mechanism involving transforming growth factor-beta. Immunology 2010, 129, 197–206.
  20. Zhang L, Jin N, Nakayama M, O’Brien RL, Eisenbarth GS, Born WK: Gamma delta T cell receptors confer autonomous responsiveness to the insulin peptide B:9–231. J Autoimmun 2010, 34, 478–484.
  21. Goldrath AW, Barber L, Chen KE, Alters SE: Differences in adhesion markers, activation markers, and TcR in islet infiltrating vs. peripheral lymphocytes in the NOD mouse. J Autoimmun 1995, 8, 209–220.
  22. Krętowski A, Myśliwiec J, Kinalska I: Abnormal distribution of gamma delta T lymphocytes in Graves’ disease and insulin-dependent diabetes type 1. Arch Immunol Ther Exp (Warsz) 2000, 48, 39–42.
  23. Zocchi MR, Ferrarini M, Migone N, Casorati G: T-cell receptor V delta gene usage by tumor reactive gamma delta T lymphocytes infiltrating human lung cancer. Immunology 1994, 81, 234–239.
  24. Zheng BJ, Ng SP, Chua DT, Sham JS, Kwong DL, Lam CK, Ng MH: Peripheral gamma delta T-cell deficit in nasopharyngeal carcinoma. Int J Cancer 2002, 99, 213–217.
  25. Szczepanik M, Gryglewski A: Limfocyty gamma delta. (Gamma-delta lymphocytes). Przegl Lek 1995, 52, 400–402.
  26. Zheng B, Lam C, Im S, Huang J, Luk W, Lau SY, Yau KK, Wong C, Yao K, Ng MH: Distinct tumour specificity and IL-7 requirements of CD56(–)and CD56(+) subsets of human gamma delta T cells. Scand J Immunol 2001, 53, 40–48.
  27. Malek TR, Yu A, Vincek V, Scibelli P, Kong L: CD4 regulatory T cells present lethal autoimmunity in IL-2R beta – deficient mice: Implications for the nonredundant function of IL-2. Immunity 2002, 17, 167–178.
  28. Testi R, D’Ambrosio D, De Maria R Santoni A: The CD69 receptor: A multipurpose cell-surface trigger for haematopoietic cells. Immunol Today 1994, 10, 479–483
  29. Cairo C, Armstrong CL, Cummings JS, Deetz CO, Tan M, Lu C, Davis CE, Pauza CD: Impact of age, gender, and race on circulating γδ T cells. Hum Immunol 2010, 71, 968–975.