Frequency of γδ T Cells and Invariant Natural Killer T Cells in Helicobacter Pylori-infected Patients with Peptic Ulcer and Gastric Cancer
-
Mojtaba Shadman
,
Zeinab Rajabian
,
Abolghasem Ajami
,
Hadi Hussein-Nattaj
,
Alireza Rafiei
,
Vahid Hosseini
,
Tarang Taghvaei
,
Ali Abbasi
,
Mohsen Tehrani
Abstract
To clarify the effect of γδ T cells and invariant Natural Killer T (iNKT) cells in pathophysiology of dyspeptic disorders, number of these two cells in patients with non-ulcer dyspepsia (NUD), peptic ulcer disease (PUD), and gastric cancer (GC) were compared.Patients with dyspepsia were divided into three groups of NUD, PUD, and GC according to their endoscopic and histopathological examinations. Helicobacter pylori infection was diagnosed by rapid urease test and histopathology. The number of peripheral blood CD3+TCRgd+ T cells and CD3+Va24Ja18+ iNKT cells were determined by flow cytometry. Immunohistochemistry (IHC) was also used for identifying the TCRgd+ cells.Forty two patients with NUD (31.6%), 44 with PUD (33.1%), and 47 with GC (35.3%) were included in the study. The frequency of CD3+TCRgd+ T cells in peripheral blood of patients with GC (2.71±0.25) was significantly lower than that in NUD (3.97±0.32, p<0.05) and PUD groups (3.87±0.32, p<0.05). However, there was no significant difference in CD3+TCRgd+ T cell percentage between the NUD and PUD groups. The frequency of TCRgd+ lymphocytes was significantly lower in tissue samples from patients with GC (4.81±0.53) than in NUD (11.09±1.09, p<0.0001) and PUD groups (11.11±1.01, p<0.0001). Also, we could not find any significant difference in the percentage of mucosal TCRgd+ cells between the NUD and PUD groups. The results showed no significant difference in iNKT cells percentage among the three groups of patients.The results suggest that decreasing number of γδ T cells may be related to development and progression of gastric cancer.
1. Rota CA, Pereira-Lima JC, Blaya C, Nardi NB. Consensus and variable region PCR analysis of helicobacter pylori 3′ region of cagA gene in isolates from individuals with or without peptic ulcer. J Clin Microbiol 2001; 39(2):606-12.
2. Xu H, Chaturvedi R, Cheng Y, Bussiere FI, Asim M, Yao MD, et al. Spermine oxidation induced by Helicobacter pylori results in apoptosis and DNA damage: implications for gastric carcinogenesis. Cancer Res 2004 ;64(23):8521-5.
3. Wilson KT, Crabtree JE. Immunology of helicobacter pylori: Insights in to the failure of the immune response and perspectives on vaccine studies. Gastroenterology 2007; 133(1):288-308.
4. Tasi HF, Hsu PN. Interplay between helicobacter pylori and immune cells in immune pathogenesis of gastric inflammation and mucosal pathology. Cell Mol immunol 2010; 7(4):255-9.
5. Robinson K, Argent RH, Atherton JC. The inflammatory and immune response to helicobacter pylori infection. Best Pract Res Clin Gastroenterol 2007;21(2):237-59.
6. Jones NL, Shannon PT, Cutz E, Yeger H, Sherman PM.Increase in proliferation and apoptosis gastric epithelial cells early in the natural history of Helicobacter pylori infection. Am J Pathol 1997; 151(6):1685–703.
7. Wagner S, Beil W, Westermann J, Logan RP, Bock CT, Trautwein C, et al. Regulation of gastric epithelial cell growth by Helicobacter pylori: offdence for a major role ofapoptosis. Gastroenterology 1997; 113(6):1836–47.
8. Rudi J, Kuck D, Strand S, von Herbay A, Mariani SM, Krammer PH, et al. Involvement of the CD95(APO-1/Fas) receptor and ligand system in Helicobacter pylori- inducedgastric epithelial apoptosis. J Clin Invest 1998;102(8):1506–14.
9. Fan XJ, Crowe SE, Behar S, Gunasena H, Ye G, Haeberle H, et al. The effect of class II major histocompatibility complex expression on adherence of Helicobacter pylori and induction ofapoptosis in gastric epithelial cells: a mechanism for T helper cell type 1-mediated damage. J Exp Med 1998; 187(10):1659–69.
10. Wu YY, Tsai HF, Lin WC, Chou AH, Chen HT, Yang JC, et al. Helicobacter pylori enhances tumor necrosis factor-related apoptosis-inducing ligand- mediatedapoptosis in human gastric epithelial cells. World J Gastroenterol 2004; 10(16):2334–39.
11. Jung HC, Kim JM, Song IS, Kim CY. Helicobacter pylori induces an array of pro-inflammatory cytokines inhuman gastric epithelial cells: quantification of mRNA for interleukin-8, -1 alpha/beta, granulocyte macrophage colony-stimulating factor, monocyte chemoattractant protein-1 and tumour necrosis factor-alpha. J Gastroenterol Hepatol 1997; 12(7):473–80.
12. Zhang Q, Dawodu JB, Etolhi G, Husain A, Gemmell CG, Russell RI. Relationship between the mucosal production of reactive oxygen radicals and density of Helicobacter pylori in patients with duodenal ulcer. Eur J Gastroenterol Hepatol 1997; 9(3):261-5.
13. Yamaoka Y, Kita M, Kodama T, Sawai N, Kashima K, Imanishi J. Induction of various cytokines and development of severe mucosal inflammation by cagA gene positive Helicobacter pylori strains. Gut 1997;41(4):442-51.
14. Trinchieri G. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 2003; 3(2):133-46.
15. Uno K, Kato K, Shimosegawa T. Novel role of toll-like receptors in Helicobacter pylori - induced gastric malignancy. World J Gastroenterol 2014; 20(18):5244-51.
16. Pinto-Santini D, Salama NR. The biology of Helicobacter pylori infection, a major risk factor for gastric adenocarcinoma. Cancer Epidemiol Biomarkers Prev 2005; 14(8):1853-8.
17. Kuroda H, Satio H, Ikeguchi M. Decreased number and reduced NKG2D expression of Vδ1 γδ T cells are involved in the impaired function of Vδ1 γδ T cells in the tissue of gastric cancer. Gastric Cancer 2012; 15(4):433–9.
18. Hayday A, Tigelaar R. Immunoregulation in the tissues by gamma delta T cells. Nat Rev Immunol 2003;3(3):233–42.
19. Newton DJ, Andrew EM, Dalton JE, Mears R, Carding SR. Identification of novel gammadelta T-cell subsets following bacterial infection in the absence of Vgamma1+ T cells: homeostatic control of gammadelta T-cell responses to pathogen infection by Vgamma1+ T cells. Infect Immun 2006; 74(2):1097–105.
20. Ferrarini M, Ferrero E, Dagna L, Poggi A, Zocchi MR.Human gammadelta T cells: a nonredundant system in the immune-surveillance against cancer. Trends Immunol 2002; 23(1):14-8.
21. Ziegler HK. The role of gamma/delta T cells in immunity to infection and regulation of inflammation. Immunol Res 2004; 29(1-3):293–302.
22. Morita CT, Jin C, Sarikonda G, Wang H. Nonpeptide antigens, presentation mechanisms, and immunological memory of human Vgamma2Vdelta2 T cells: discriminating friend from foe through the recognition of prenyl pyrophosphate antigens. Immunol Rev 2007; 215:59-76.
23. Futagami S, Hiratsuka T, Suzuki K, Kusunoki M, Wada K, Miyake K, et al. gammadelta T cells increase with gastric mucosal interleukin (IL)-7, IL-1beta, and Helicobacter pylori urease specific immunoglobulin levels via CCR2 upregulation in Helicobacter pylori gastritis. J Gastroenterol Hepatol 2006; 21(1 pt 1):32-40.
24. Molling JW, Kölgen W, van der Vliet HJ, Boomsma MF, Kruizenga H, Smorenburg CH, et al. Peripheral blood IFN-gamma-secreting Valpha24+Vbeta11+ NKT cell numbers are decreased in cancer patients independent of tumor type or tumor load. Int J Cancer 2005; 116(1):87-93.
25. Dellabona P, Padovan E, Casorati G, Brockhaus M, Lanzavecchia A. An invariant V alpha 24-J alpha Q/V beta 11 T cell receptor is expressed in all individuals by clonally expanded CD4-8- T cells. J Exp Med 1994;180(3):1171-6.
26. Scheuplein F, Thariath A, Macdonald S, Truneh A, Mashal R, Schaub R. A humanized monoclonal antibody specific for invariant Natural Killer T (iNKT) cells for in vivo depletion. PLoS One 2013; 8(9):e76692.
27. Ito Y, Vela JL, Matsumura F, Hoshino H, Tyznik A, Lee H, et al. Helicobacter pylori cholesterylα-glucosides contribute to its pathogenicity and immune response by naturalkiller T cells. PLoS One 2013; 8(9):e78191.
28. Rosai J, Ackerman LV. The pathology of tumors, part III:grading, staging & classification. CA Cancer J Clin 1979;29(2):66-77.
29. Inman BA, Frigola X, Harris KJ, Kuntz SM, Lohse CM, Leibovich BC, et al. Questionable relevance of gamma delta T lymphocytes in renal cell carcinoma. J Immunol 2008; 180(5):3578-84.
30. Kowalczyk D, Skorupski W, Kwias Z, Nowak J.Activated gamma/delta T lymphocytes infiltrating renal cell carcinoma. Immunol Lett 1996; 53(1):15-8.
31. Kobayashi H, Tanaka Y, Yagi J, Toma H, Uchiyama T.Gamma/delta T cells provide innate immunity against renal cell carcinoma. Cancer Immunol Immunother 2001;50(3):115-24.
32. Lee AJ, Kim SG, Chae HD, Lee GH, Shin IH. γδ T cells are increased in the peripheral blood of patients with gastric cancer. Clin Chim Acta 2012; 413(19-20):1495-9.
33. Ma C, Zhang Q, Ye J, Wang F, Zhang Y, Wevers E, et al.Tumor-infiltrating γδ T lymphocytes predict clinical outcome in human breast cancer. J Immunol 2012;189(10):5029-36.
34. Rudnicka K, Włodarczyk M, Moran AP, Rechciński T, Miszczyk E, Matusiak A, et al. Helicobacter pylori antigens as potential modulators of lymphocytes' cytotoxic activity. Microbiol Immunol 2012; 56(1):62-75.
35. Motohashi S, Kobayashi S, Ito T, Magara KK, Mikuni O, Kamada N, et al. Preserved IFN-alpha production of circulating Valpha24 NKT cells in primary lung cancer patients. Int J Cancer 2002; 102:159–65.
36. Yanagisawa K, Seino K, Ishikawa Y, Nozue M, Todoroki T, Fukao K. Impaired proliferative response of V alpha 24 NKT cells from cancer patients against alpha- galactosylceramide. J Immunol 2002; 168(12):6494–9.
37. Tahir SM, Cheng O, Shaulov A, Koezuka Y, Bubley GJ, Wilson SB, et al. Loss of IFN-gamma production by invariant NK T cells in advanced cancer. J Immunol 2001; 167(7):4046–50.
38. Kasper HU, Drebber U, Zur HA, Stippel D, Dienes HP, Dries V. Dominance of CD4 alpha/beta T-cells and inferior role of innate immune reaction in liver metastases. Anticancer Res 2003; 23(4):3175–81.
39. Kenna T, Mason LG, Porcelli SA, Koezuka Y, Hegarty JE, O’Farrelly C, et al. NKT cells from normal and tumor-bearing human livers are phenotypically and functionally distinct from murine NKT cells. J Immunol 2003; 171(4):1775–9.
40. Motohashi S, Ishikawa A, Ishikawa E,Otsuji M, Iizasa T, Hanaoka H, et al. Phase I study of in vitro expanded natural killer T cells in patients with advanced and recurrent non-small cell lung cancer. Clin Cancer Res 2006; 12:6079-86.
41. Nieda M, Okai M, Tazbirkova A, Lin H, Yamaura A, Ide K, et al. Therapeutic activation of Valpha24 Vbeta11 NKT cells in human subjects results in highly coordinated secondary activation of acquired and innate immunity. Blood 2004; 103(2):383–9.
| Files | ||
| Issue | Vol 14, No 5 (2015) | |
| Section | Original Article(s) | |
| Keywords | ||
| Antigen Helicobacter pylori Invariant Natural Killer T Cells Peptic Ulcer Receptor Stomach Neoplasms T-Cell gamma-delta | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
