Regulatory T cells percentage in peripheral blood before and after eradication of Helicobacter pylori

Yuka Satoh, Hatsue Ogawara, Osamu Kawamura, Yasuyuki Shimoyama, Motoyasu Kusano, Akihiko Yokohama, Takayuki Saitoh, Hiroshi Handa, Norifumi Tsukamoto, Hirokazu Murakami

Department of Blood Transfusion Service, Gunma University Hospital, Maebashi, Japan.
Department of Endoscopy and Endoscopic Surgery, Gunma University Hospital, Maebashi, Japan.
Department of Laboratory Sciences, Course of Health Sciences, Gunma Graduate School of Health Sciences, Maebashi, Japan.
Department of Medicine and Clinical Science, Gunma Graduate School of Medicine, Maebashi, Japan.
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan.
Faculty of Health Sciences, Gunma Paz College, Takasaki, Japan.
Oncology Center, Gunma University Hospital, Maebashi, Japan.

DOI: 10.4236/health.2014.64035                

Abstract

Helicobacter pylori (H. pylori) induces gastroduodenal diseases and vigorous humural and cellular immune abnormalities. In order to clarify the immunological changes before and after eradication of H. pylori, the percentages and ratios of the following cells in the peripheral blood of 32 H. pylori-infected patients and 25 control subjects were analyzed: CD4+ T cells, CD8+ T cells, T helper 1 cells (Th1), T helper 2 cells (Th2), CD4+CD25+ T cells, Foxp3+ regulatory T cells (Treg), CD4/CD8 ratio, and Th1/Th2 ratio. CD4/CD8 ratio was significantly higher in H. pylori-infected patients before (mean ± SD, 2.9 ± 1.9) and after (mean ± SD, 2.8 ± 1.6) eradication of H. pylori than in control subjects (mean ± SD, 2.1 ± 0.9). The percentage of Th2 cells was significantly higher in H. pylori-infected patients (mean ± SD, 2.6 ± 1.1) than in control subjects (mean ± SD, 1.9 ± 1.1; p < 0.02). The percentage of Th2 cells after eradication of H. pylori (mean ± SD, 2.3 ± 1.4) was lower than that before eradication. There was no significant difference between control subjects (mean ± SD, 4.1% ± 1.5%) and patients before H. pylori eradication (mean ± SD, 4.5% ± 2.4%) in the percentage of Tregs, but the percentage was significantly higher in patients after H. pylori eradication (mean ± SD, 5.2% ±2.6%) than in control subjects. The function of peripheral induced Tregs was reported to suppress the excessive immune reaction in chronic inflammation. These data suggest that Tregs may proliferate and be activated to suppress the activation of humoral immunity in H. pylori-infected patients, and these changes continue after 3 months or later of successful eradication of H. pylori.

Keywords

Helicobacter pylori; Regulatory T Cell; Th1 Cell; Th2 Cell

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Megraud, F. and Lamouliatte, H. (1992) Helicobacter and duodenal ulcer. Digestive Diseases and Sciences, 37, 769-772. http://dx.doi.org/10.1007/BF01296437
[2]	Parsonnet, J., Freidman, G.D. and Vandersteen D.P. (1991) Helicobacter pylori infection and the risk of gastric carcinoma. The New England Journal of Medicine, 325, 1127-1131. http://dx.doi.org/10.1056/NEJM199110173251603
[3]	Parsonnet, J., Hansen, S. and Rodriguez, L. (1994) Helicobacter pylori infection and gastric lymphoma. The New England Journal of Medicine, 330, 1267-1271. http://dx.doi.org/10.1056/NEJM199405053301803
[4]	Fan, X.J., Chua, A., Shahi, C.N., McDevitt, J., Keeling, P.W. and Kelleher, D. (1994) Gastric T lymphocyte responses to Helicobacter pylori in patients with H. pylori colonization. Gut, 35, 1379-1384. http://dx.doi.org/10.1136/gut.35.10.1379
[5]	D’Elios, M.M., Manghetti, M., Almerigogna, F., Amedei, A., Costa, F. Burroni, D., et al. (1997) Different cytokine profile and antigen-specificity repertoire in Helicobacter pylori-specific T cell clones form the antrum of chronic gastritis patients with or without peptic ulcer. European Journal of Immunology, 27, 1750-1755. http://dx.doi.org/10.1002/eji.1830270723
[6]	Kayhan, B., Araslin, M., Eren, H., Aydemir, S., Kayhan, B. and Aktas, E. (2008) Analysis of peripheral blood lymphocyte phenotype and Th1/Th2 cytokines profile in the systemic immune responses of Helicobacter pylori-infected individuals. Microbiology and Immunology, 52, 531-538. http://dx.doi.org/10.1111/j.1348-0421.2008.00066.x
[7]	Yuceyar, H., Kokuludag, A., Tezioglu, E., Goksei, G. and Isisag, A. (2002) The systemic cellular immune response in the Helicobacter pylori-associated duodenal ulcer and chronic antral gastritis. Hepatogastroenterology, 49, 1177-1179.
[8]	Soares, T.F., Rocha, G.A., Rocha, A.M.C., Correa-Oliveira, R., Martins-Filho, O.A., Carvalhos, A.S.T., et al. (2005) Phenotypic study of peripheral blood lymphocytes and humoral immune response in Helicobacter pylori infection according age. Scandinavian Journal of Immunology, 62, 63-70. http://dx.doi.org/10.1111/j.1365-3083.2005.01638.x
[9]	Satoh, Y., Ogawara, H., Kawamura, O., Kusano, M. and Murakami, H. (2012) Clinical significance of peripheral blood T lymphocyte subsets in Helicobacter pylori-infected patients. Gastroenterology Research and Practice, 2012, Article ID: 819842. http://dx.doi.org/10.1155/2012/819842
[10]	El Miedany, Y.M., Baddour, M., Ahmed, I. and Fahmy, H. (2005) Sjogren’s syndrome: Concomitant H. pylori infection and possible correlation with clinical parameters. Joint Bone Spin, 72, 135-141. http://dx.doi.org/10.1016/j.jbspin.2004.04.005
[11]	Radic, M., Kaliterna, D.M. and Radic, J. (2010) Helicobacter pylori infection and systemic sclerosis-is there a link? Joint Bone Spine, 78, 337-340. http://dx.doi.org/10.1016/j.jbspin.2010.10.005
[12]	Stasi, R., Sarpatwari, A., Segal, J.B., Osborn, J., Evangelista, M.L., Cooper, N., et al. (2009) Effects of eradication of Helicobacter pylori infection in patients with immune thrombocytopenic purpura: A systemic review. Blood, 113, 1231-1240. http://dx.doi.org/10.1182/blood-2008-07-167155
[13]	Basi, V., Santinelli, C., Lengo, A. and Romano, C. (2010) Identification of a correlation between Helicobacter pylori infection and Graves’ disease. Helicobacter, 15, 558-562. http://dx.doi.org/10.1111/j.1523-5378.2010.00802.x
[14]	Jesnowski, R., Isaksson, B., Mohrchke, C., Bertsch, C., Bulajic, M., Schneider-Brachert, W., et al. (2010) Helicobacter pylori in autoimmune pancreatitis and pancreatic carcinoma. Pancreatology, 10, 462-466. http://dx.doi.org/10.1159/000264677
[15]	Murakami, H., Yamane, A., Sawamura, M., Matsumoto, M., Murayama, K., Shimano, S., et al. (2005) High Th1/ Th2 ratio in patients with multiple myeloma. Leukemia Research, 29, 135-140. http://dx.doi.org/10.1016/j.leukres.2004.06.003
[16]	Hamdi, W., Ogawara, H., Handa, H., Tsukamoto, N., Nojima, Y. and Murakami, H. (2009) Clinical significance of regulatory T cells in patients with myelodysplastic syndrome. European Journal of Haematology, 82, 201-207. http://dx.doi.org/10.1111/j.1600-0609.2008.01182.x
[17]	Kodama, M., Murakami, K., Okimoto, T., Sato, R., Uchida, M., Abe, T., et al. (2012) Ten-year prospective follow-up of histological changes at five points on the gastric mucosa as recommended by the updated Sydney system after Helicobacter pylori eradication. Journal of Gastroenterology, 47, 394-403. http://dx.doi.org/10.1007/s00535-011-0504-9
[18]	Watanabe, Hm, Yamaguchi, Nm, Kuwayama, H., Sekinem C, Uemuram N., Kaise, M., et al. (2003) Improvement in gastric histology following Helicobacter pylori eradication therapy in Japanese peptic ulcer patients. Journal of International Medical Research, 31, 362-369. http://dx.doi.org/10.1177/147323000303100502
[19]	Fichman, S. and Niv, Y. (2994) Histological changes in the gastric mucosa after Helicobacter pylori eradication. European Journal of Gastroenterology & Hepatology, 16, 1183-1188. http://dx.doi.org/10.1097/00042737-200411000-00017
[20]	Kondo, Y., Joh, T., Sasaki, M., Oshima, T., Itoh, K., Tanida, S., et al. (2004) Helicobacter pylori eradication decreases blood neutrophil and monocyte counts. Alimentary Pharmacology & Therapeutics, 20, 74-79. http://dx.doi.org/10.1111/j.1365-2036.2004.01988.x
[21]	Karttunen, T.J., Niemela, S. and Kerola, T. (1996) Blood leukocyte differential in Helicobacter pylori infection. Digestive Diseases and Sciences, 41, 1332-1336. http://dx.doi.org/10.1007/BF02088556
[22]	Mills, K.H. (2004) Regulatory T cells: Friend or foe in immunity to infection? Nature Reviews Immunology, 4, 841-855. http://dx.doi.org/10.1038/nri1485
[23]	Lundgren, A., Strömberg, E., Sjöling, A., Lindholm, C., Enarsson, K., Edebo, A., et al. (2005) Mucosal Foxp3-expressing CD4+CD25high regulatory T cells in Helicobacter pylori-infected patients. Infection and Immunity, 73, 523-531. http://dx.doi.org/10.1128/IAI.73.1.523-531.2005
[24]	Perrone, G., Ruffini, P.A., Catalano, V., Spino, C., Santini, D., Muretto, P., et al. (2008) Intratumoural Foxp3-positive regulatory T cells are associated with adverse prognosis in radically resected gastric cancer. European Journal of Cancer, 44, 1875-1882. http://dx.doi.org/10.1016/j.ejca.2008.05.017
[25]	Kindlund, B., Sjöling, A., Hansson, M., Edebo, A., Hanson, L.E., Sjövall, H., et al. (2009) 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, 14, 192-201. http://dx.doi.org/10.1111/j.1523-5378.2009.00673.x
[26]	Chen, T., Jin, R., Huang, Z., Hong, W., Chen, Z. and Wang, J. (2010) The variation of expression of CD4+ CD25+ Foxp3+ regulatory T cells in patients with Helicobacter pylori infection and eradication. Hepatogastroenterology, 57, 430-435.
[27]	Lundgren, A., Suri-Payer, E., Enarsson, K., Svennerholm, A.-M. and Lundin, B.S. (2003) Helicobacter pylori-specific CD4+ CD25high regulatory T cells suppress memory T-cell responses to H. pylori in infected individuals. Infection and Immunity, 71, 1755-1762. http://dx.doi.org/10.1128/IAI.71.4.1755-1762.2003