Clinical Significance of Peripheral Blood T Lymphocyte Subsets in Helicobacter pylori-Infected Patients

Yuka Satoh, Hatsue Ogawara, Osamu Kawamura, Motoyasu Kusano, Hirokazu Murakami, Yuka Satoh, Hatsue Ogawara, Osamu Kawamura, Motoyasu Kusano, Hirokazu Murakami

Abstract

Background. Helicobacter pylori chronically colonizes gastric/duodenal mucosa and induces gastroduodenal disease and vigorous humoral and cellular immune responses. Methods. In order to clarify the immunological changes induced by this infection, we determined the percentage and, as indicated, ratios of the following cells in peripheral blood of 45 H. pylori-infected patients and 21 control subjects: CD4(+) T cell, CD8(+) T cells, T helper 1 cells (Th1), T helper 2 cells (Th2), CD4(+)CD25(+) T cells, Foxp3(+) regulatory T cells (Tregs), CD4/CD8 ratio, and Th1/Th2 ratio. Results. The percentage of CD8(+) T cells was significantly lower in H. pylori-infected patients (mean ± SD; 18.0 ± 7.1%) compared to control subjects (mean ± SD; 23.2 ± 7.8%) (P < 0.05). The CD4/CD8 ratio was significantly higher in H. pylori-infected patients (mean ± SD; 3.1 ± 2.4) compared to control subjects (mean ± SD; 2.1 ± 1.0) (P < 0.05). The Th1/Th2 ratio was significantly lower in H. pylori-infected patients (mean ± SD; 10.0 ± 8.5) compared to control subjects (mean ± SD; 14.5 ± 9.0) (P < 0.05). The percentage of CD4(+)CD25(+) T cells in H. pylori-infected patients (mean ± SD; 13.2 ± 6.2%) was significantly higher than that in control subjects (mean ± SD; 9.8 ± 3.4%) (P < 0.05). However, there was no significant difference in Tregs. Conclusion. Tregs did not decrease, but the activation of humoral immunity and Th2 polarization were observed in the peripheral blood of H. pylori-infected patients. In some cases, these changes may induce systemic autoimmune diseases.

Figures

Figure 1
Figure 1
(a) Comparison of the percentage of CD4+ and CD8+ T cells. Left and right sides show the data of control subjects and H. pylori-infected patients, respectively. White columns represent the percentage of CD4+ T lymphocyte, and black columns represent CD8+ T lymphocyte. Data are given as mean ± SD. There was no significant difference in the percentage of CD4+ T cells in H. pylori-infected patients (mean ± SD; 43.0 ± 10.4%) as compared to control subjects (mean ± SD; 42.2 ± 8.1%). However, the percentage of CD8+ T cells was significantly lower in H. pylori-infected patients (mean ± SD; 18.0 ± 7.1%) compared to control subjects (mean ± SD; 23.2 ± 7.8%) (P < 0.05). (b) CD4/CD8 ratio in control subjects (white column) and H. pylori-infected patients (black column). Data are given as mean ± SD. The CD4/CD8 ratio was significantly higher in H. pylori-infected patients (mean ± SD; 3.1 ± 2.4) compared to control subjects (mean ± SD; 2.1 ± 1.0) (P < 0.05).
Figure 2
Figure 2
(a) The percentage of Th1 cells and Th2 cells. Left and right figures show the percentage of Th1 and Th2 cells, respectively. White columns represent the data of normal subjects, and black columns represent the data of H. pylori-infected patients. Data are given as mean ± SD. There was no significant difference in the percentage of Th1 cells in H. pylori-infected patients (mean ± SD; 20.2 ± 8.6%) and control subjects (mean ± SD; 21.2 ± 10.6%). However, the percentage of Th2 cells in H. pylori-infected patients (mean ± SD; 2.8 ± 1.6%) was significantly higher than in control subjects (mean ± SD; 1.8 ± 1.0%), (P < 0.05). (b) Comparison of Th1/Th2 ratio. White columns represent the data of normal subjects, and black columns represent the data of H. pylori-infected patients. Data are given as mean ± SD. The Th1/Th2 ratio was significantly lower in H. pylori-infected patients (mean ± SD; 10.0 ± 8.5) compared to control subjects (mean ± SD; 14.5 ± 9.0) (P < 0.05).
Figure 3
Figure 3
The percentage of CD4+CD25+ T cell and CD4+CD25+Foxp3+ (regulatory T cell). Left and right sides show the data of control subjects and H. pylori-infected patients, respectively. White columns represent the percentage of CD4+CD25+ T cell, and black columns represent the percentage of regulatory T cell. Data are given as mean ± SD. The percentage of CD4+CD25+ T cells in H. pylori-infected patients (mean ± SD; 13.2 ± 6.2%) was significantly higher than that in control subjects (mean ± SD; 9.8 ± 3.4%) (P < 0.05). The percentage of Tregs (CD4+CD25+Foxp3+ T cells) was not significantly different between H. pylori-infected patients (mean ± SD; 4.1 ± 2.1%) and control subjects (mean ± SD; 4.0 ± 1.7%).

References

    1. Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. The Lancet. 1984;1(8390):1311–1314.
    1. Taylor DN, Blaser MJ. The epidemiology of Helicobacter pylori infection. Epidemiologic Reviews. 1991;13:42–59.
    1. Megraud F, Lamouliatte H. Helicobacter pylori and duodenal ulcer. Evidence suggesting causation. Digestive Diseases and Sciences. 1992;37(5):769–772.
    1. Parsonnet J, Friedman GD, Vandersteen DP, et al. Helicobacter pylori infection and the risk of gastric carcinoma. The New England Journal of Medicine. 1991;325(16):1127–1131.
    1. Parsonnet J, Hansen S, Rodriguez L, et al. Helicobacter pylori infection and gastric lymphoma. The New England Journal of Medicine. 1994;330(18):1267–1271.
    1. Kondo Y, Joh T, Sasaki M, et al. Helicobacter pylori eradication decreases blood neutrophil and monocyte counts. Alimentary Pharmacology and Therapeutics, Supplement. 2004;20(1, supplement):74–79.
    1. Karttunen TJ, Niemelä S, Kerola T. Blood leukocyte differential in Helicobacter pylori infection. Digestive Diseases and Sciences. 1996;41(7):1332–1336.
    1. Kayhan B, Araslin M, Eren H, et al. Analysis of peripheral blood lymphocyte phenotypes and Th1/Th2 cytokines profile in the systemic immune responses of Helicobacter pylori infected individuals. Microbiology and Immunology. 2008;52(11):531–538.
    1. Yuceyar H, Saruc M, Kokuludag A, Terzioglu E, Goksel G, Isisag A. The systemic cellular immune response in the Helicobacter pylori-associated duodenal ulcer and chronic antral gastritis. Hepato-Gastroenterology. 2002;49(46):1177–1179.
    1. Soares TF, Rocha GA, Rocha AMC, et al. Phenotypic study of peripheral blood lymphocytes and humoral immune response in Helicobacter pylori infection according to age. Scandinavian Journal of Immunology. 2005;62(1):63–70.
    1. Fan XJ, Chua A, Shahi CN, McDevitt J, Keeling PWN, Kelleher D. Gastric T lumphocyte responses to Helicobacter pylori in patients with H pylori colonisation. Gut. 1994;35(10):1379–1384.
    1. D’Elios MM, Manghetti M, Almerigogna F, et al. Different cytokine profile and antigen-specificity repertoire in Helicobacter pylori-specific T cell clones from the antrum of chronic gastritis patients with or without peptic ulcer. European Journal of Immunology. 1997;27(7):1751–1755.
    1. Sakaguchi S, Sakaguchi N, Shimizu J, et al. Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunological Reviews. 2001;182:18–32.
    1. Winger EE, Reed JL. Low circulating CD4+CD25+Foxp3+ T regulatory cell levels predict miscarriage risk in newly pregnant women with a history of failure. American Journal of Reproductive Immunology. 2011;66(4):320–328.
    1. Lundgren A, Strömberg E, Sjoling A, et al. Mucosal FOXP3-expressing CD4+ CD25high regulatory T cells in Helicobacter pylori-infected patients. Infection and Immunity. 2005;73(1):523–531.
    1. Perrone G, Ruffini PA, Catalano V, et al. Intratumoural FOXP3-positive regulatory T cells are associated with adverse prognosis in radically resected gastric cancer. European Journal of Cancer. 2008;44(13):1875–1882.
    1. Kindlund B, Sjöling A, Hansson M, et al. FOXP3-expressing CD4+ T-cell numbers increase in areas of duodenal gastric metaplasia and are associated to CD4+ T-cell aggregates in the duodenum of Helicobacter pylori-infected duodenal ulcer patients. Helicobacter. 2009;14(3):192–201.
    1. Chen T, Jin R, Huang Z, Hong W, Chen Z, Wang J. The variation of expression of CD4+ CD25+ Foxp3 + regulatory T cells in patients with Helicobacter pylori infection and eradication. Hepato-Gastroenterology. 2010;57(99-100):430–435.
    1. Radić M, Kaliterna DM, Radić J. Helicobacter pylori infection and systemic sclerosis-is there a link? Joint Bone Spine. 2011;78(4):337–340.
    1. Bassi V, Santinelli C, Iengo A, Romano C. Identification of a Correlation between Helicobacter pylori Infection and Graves’ Disease. Helicobacter. 2010;15(6):558–562.
    1. Jesnowski R, Isaksson B, Möhrcke C, et al. Helicobacter pylori in autoimmune pancreatitis and pancreatic carcinoma. Pancreatology. 2010;10(4):462–466.
    1. Hood CJ, Lesna M. Immunocytochemical quantitation of inflammatory cells associated with Helicobacter pylori infection. British Journal of Biomedical Science. 1993;50(2):82–88.
    1. Nurgalieva ZZ, Conner ME, Opekun AR, et al. B-cell and T-cell immune responses to experimental Helicobacter pylori infection in humans. Infection and Immunity. 2005;73(5):2999–3006.
    1. Bamford KB, Fan X, Crowe SE, et al. Lymphocytes in the human gastric mucosa during Helicobacter pylori have a T helper cell 1 phenotype. Gastroenterology. 1998;114(3):482–492.
    1. Dejaco C, Duftner C, Schirmer M. Are regulatory T-cells linked with aging? Experimental Gerontology. 2006;41(4):339–345.
    1. Rosenkranz D, Weyer S, Tolosa E, et al. Higher frequency of regulatory T cells in the elderly and increased suppressive activity in neurodegeneration. Journal of Neuroimmunology. 2007;188(1-2):117–127.
    1. Gregg R, Smith CM, Clark FJ, et al. The number of human peripheral blood CD4+ CD25high regulatory T cells increases with age. Clinical and Experimental Immunology. 2005;140(3):540–546.
    1. Luther C, Poeschel S, Varga M, Melms A, Tolosa E. Decreased frequency of intrathymic regulatory T cells in patients with myasthenia-associated thymoma. Journal of Neuroimmunology. 2005;164(1-2):124–128.
    1. Lundgren A, Suri-Payer E, Enarsson K, Svennerholm AM, Lundin BS. Helicobacter pylori-specific CD4+ CD25high regulatory T cells suppress memory T-cell responses to H. pylori in infected individuals. Infection and Immunity. 2003;71(4):1755–1762.

Source: PubMed

3
Suscribir