Immunohistochemical Investigation of the role of Foxp3+ T regulatory cells in patients with Inflammatory Bowel Disease complicated by Cytomegalovirus infection in colon

Immunohistochemical Investigation of the role of Foxp3+ T regulatory cells in patients with Inflammatory Bowel Disease complicated by Cytomegalovirus infection in colon

Despoina Antaraki, Georgios Kakiopoulos, Sophia Pappa, Georgia-Heleni Thomopoulou, Eirini Thimara, Aliki Liakea, Andreas Lazaris




Aim: We attempted to study whether the presence of T-regulatory cells in tissues obtained from patients with an inflammatory bowel disease are augmented when Cytomegalovirus coexists in the bowel. Experimental data were analysed using statistical methods and were combined with bibliographical references in order to investigate the role of T-reg cells in immunodeficient patients with or without CMV infection.

Materials and Methods: Sixty-one cases of inflammatory bowel disease were divided into two groups. The first one included patients with either Crohn’s disease or ulcerative colitis that co-existed with CMV bowel infection, whereas the second group (control group) consisted of patients with inflammatory bowel disease without CMV infection. Sections from formalin-fixed, paraffin-embedded tissues were immunohistochemically elaborated with CMV-specific polyclonal antibodies and the stained slides were evaluated in order to define Foxp3 protein levels and the attendance of Tregs in specific tissues.

Results: Statistical analysis of the evaluated samples revealed statistically significant correlation between the presence of CMV and the number of Tregs in bowel tissue. There was no evidence that CMV is related with acute phases of inflammatory bowel disease. Tregs were diminished in patients with disease in recession. The attendance of eosinophils was also examined and the results proved the existence of statistically significant correlation between the number of eosinophils and Tregs number in the examined samples.

Conclusions: Our investigation provides strong evidence that the increase of Treg population in colon mucosa is probably an underlying defensive mechanism of the human organism in order to control and suppress the local inflammatory reaction caused by infectious factors in immune deficient patients. Further study could help to shed light on the suppressive potency of Tregs and the potential value in clinical therapeutics.


Inflammatory Bowel Disease, Cytomegalovirus, T regulatory cells, Foxp3, Immunohistochemistry

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Khalid Bin Dhuban, Mara Kornete, Edward Mason, Ciriaco Piccirillo. Functional dynamics of Foxp3+ regulatory T cells in mice and humans. Immunological Reviews. April 09, 2014, p. 14.

Rudensky, Alexander. Regulatory T cells and Foxp3. Immunological Reviews. May 2011, pp. 260-268.

Pushpa Pandiyan, Jinfang Zhu. Origin and functions of pro-inflammatory cytokine producing Foxp3 regulatory T cells. Cytokine. November 2015, pp. 13-24.

Lord JD, Valliant-Saunders K, Hahn H, Thirlby RC, ZieglerSF. Paradoxically increased Foxp3+ T cells in IBD do not preferentially express the isoform of Foxp3 lacking exon 2. Digestive Diseases and Science. November, November 2012, Vol. 57, 11, pp. 2846-55.

Uhlig HH, Coombes J, Mottet C, Izcue A, Thompson C, Fanger A, et al. Characterization of Foxp3+CD4+CD25+ and IL-10 secreting CD4+CD25+ T cells during cure of colitis. Journal of Immunology. November 1, 2006, pp. 5852-60.

Saruta M, Yu QT, Fleshner PR, Mantel PY, Schmidt-Weber CB, Banham AH, et al. Characterization of Foxp3+CD4+ regulatory T cells in Crohn's disease. Clinical Immunology. December 2007, pp. 281-90.

Yu QT, Saruta M, Avanesyan A, Fleshner PR, Banham AH, Papadakis KA. Expression and functional characterization of Foxp3+CD4+ regulatory T cells in ulcerative colitis. Inflammatory Bowel Disease. February 2007, pp. 191-9.

Raed Al-Zafiri, Adrian Cologan, Polymnia Galiatsatos, Andrew Szilagyi. Cytomegalovirus complicating inflammatory bowel disease. Gastroenterology & Hepatology Volume 8. April 2012, 4, pp. 230-239.

Nicolas Leveque, Hedia Brixi-Benmansour, Thierry Reig, Fanny Renois, Deborah Talmud, Veronique Brodard et al. Low frequency of Cytomegalovirus infection during exacerbations of inflammatory bowel disease. Journal of Medical Virology. 2010, pp. 1694-1700.

Rafailidis Pl, Mourtzoukou EG, VarboritisIC, Falagas ME. Severe cytomegalovirus infection in apparently immunocompetent patients: a systematic review. Virol Journal. 2008, 27, pp. 47-54.

Onyeagocha C, Hossain MS, Kumar A, Jones RM, Roback J, Gewirtz AT. Latent cytomegalovirus infection exacerbates experimental colitis. The American Journal of Pathology. 2009, 175, pp. 2034-2042.

Cebula A, Seweryn M, Rempala GA, Pabla SS, McIndoe RA, Denning TL et al. Thymus-derived regulatory T cells contibute to tolerance to commensal microbiota. Nature. 2013, 497, pp. 258-62.

Lord J, Shows D, Chen J, Thirlby R. Human Blood and Mucosal Regulatory T cells express activation markers and inhibitory receptors in inflammatory bowel disease. Plos One. August 25, 2015, p. 11.

Rieger K, Loddenkemper C, Maul J, Fietz T, Wolff D, Terpe H et al. Mucosal Foxp3+ regulatory T cellsare numerically deficient in acute and chronic GvHD. Blood. February 15, 2006, Vol. 107, 4, pp. 1721-1722.

Taylor PA, Less CJ, Blazar BR. The infusion of ex vivo activated and expanded CD4+CD25+ immune regulatory cells inhibits graft-versus-host disease lethality. Blood. 2002, 99, pp. 3493-3499.

Hanash AM, Levy RB. Donor CD4+CD25+ T cells promote engraftment and tolerance following MHC-mismatch hematopoietic cell transplantation. Blood. 2005, 105, pp. 1828-1836.

Li L, Boussiotis VA. The role of IL-17-producing Foxp3+CD4+ T cells in inflammtory bowel disease and colon cancer. Clinical Immunology. 2013, 148, pp. 246-53.

Lord J, Chen J, Kozarek R. A case of fatal idiopathic enteritis and multiple opportunistic infections associated with dendritic cell deficiencies. Journal of Gastrointestinal and Liver Diseases. March 2013, Vol. 22, pp. 87-91.

Tan YF, Yu SJ, Wang J, Li SJ. Role of Treg/Th17 balance in the pathogenesis of cytomegalovirus infection. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. June 28, 2012, pp. 649-51.


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