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Microscopic colitis patients have increased frequencies of Ki67+proliferating and CD45RO+ active/memory CD8+ and CD4+8mucosal T cells
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.ORCID iD: 0000-0002-2244-9816
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Dept. of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
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2013 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 7, no 9, p. 694-705Article in journal (Refereed) Published
Abstract [en]

Background: Collagenous colitis (CC) and lymphocytic colitis (LC) are chronic inflammatory bowel disorders of unknown etiology. This study investigated phenotypic characteristics of the mucosal lymphocytes in CC and LC.

Methods: Lamina propria and intraepithelial lymphocytes (LPLs, IELs) isolated from mucosal biopsies from CC (n = 7), LC (n = 6), as well as LC or CC patients in histopathological remission, (LC-HR) (n = 6) and CC-HR (n = 4) and non-inflamed controls (n = 10) were phenotypically characterized by four-color flow cytometry.

Results: The proportions of CD8+ IELs were increased in CC and LC (p < 0.01) compared to controls. Increased proportions of CD45RO+CD8+ IELs and LPLs were observed in LC and even more in CC patients (p < 0.01). Both CC (p < 0.05) and LC patients had elevated proportions of CD4+8+ IELs and LPLs compared to controls. The proportions of CD45RO+ cells were increased in CD4+8+ IELs and LPLs (p < 0.05) in CC and LC patients compared to controls. Both CC (p < 0.05) and LC patients had higher proportions of Ki67+CD8+ IELs and LPLs compared to controls.

In contrast, decreased proportions of CD4+ LPLs were observed in CC and LC as well as CD4+ IELs in LC compared to controls. Increased proportions of Ki67+CD4+ IELs and LPLs (p < 0.05) were observed in CC and LC patients. CC-HR but not LC-HR patients demonstrated normalized proportions of both IELs and LPLs compared to CC and LC patients respectively.

Conclusion: LC and CC patients have differences in mucosal lymphocyte subsets, with increased proportions of Ki67+ and CD45RO+ CD8+ and CD4+8+ mucosal T cells.

Place, publisher, year, edition, pages
Oxford, United Kingdom: Oxford University Press, 2013. Vol. 7, no 9, p. 694-705
Keywords [en]
Collagenous colitis, Lymphocytic colitis, Flow cytometry, Lamina propria lymphocytes, Intraepithelial lymphocytes
National Category
Medical and Health Sciences Gastroenterology and Hepatology
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-25588DOI: 10.1016/j.crohns.2012.08.014ISI: 000323995900002PubMedID: 22995775OAI: oai:DiVA.org:oru-25588DiVA, id: diva2:548250
Available from: 2012-08-30 Created: 2012-08-30 Last updated: 2019-03-26Bibliographically approved
In thesis
1. Adaptive immune response in the intestinal mucosa of microscopic colitis patients
Open this publication in new window or tab >>Adaptive immune response in the intestinal mucosa of microscopic colitis patients
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Microscopic colitis (MC) is a chronic diarrhoeal disease of unknown aetiology, comprising collagenous colitis (CC) and lymphocytic colitis (LC). The nature of the adaptive local immune responses in the mucosa of MC patients is however far from elucidated. The present study investigates phenotypic and functional characteristics of the adaptive local immune responses in the colonic mucosa of these patients.

Our immunohistochemistry and flow cytometry studies (Paper I & II) demonstrated increased frequencies of CD8+ T cells in the colonic epithelium and lamina propria of both LC and CC patients compared to controls, whereas the frequencies of CD4+ T cells were unaltered or reduced. Our flow cytometry data revealed increased local activation of both CD4+ and CD8+ T cells in the lamina propria as well as the intraepithelial compartment of CC and LC patients compared to controls, demonstrated as increased proportions of these cells expressing the active/memory marker CD45RO and the proliferation marker Ki67.

Analysis of recent thymic emigrants by measuring T cell receptor excision circle (TREC) levels in the colonic mucosa of CC and LC patients revealed reduced TRECs levels in these patients compared to controls (Paper III). These results suggests that the observed increased numbers of T cells in the mucosa of CC and LC patients is due to the expansion of local resident T cells rather than direct recruitment of recent thymic emigrants to the mucosa.

Molecular analysis of T helper (Th) cell and cytotoxic T lymphocyte (Tc) mucosal cytokines at messenger and protein levels in the colonic biopsies from CC and LC patients demonstrated a mixed Th17/Tc17 and Th1/Tc1 mucosal cytokine profile and revealed significant differences in the mucosal cytokine levels in CC and LC patients compared to controls (Paper IV).

Finally, we have set up an in vitro model to investigate how the colonic milieu affects the activation and differentiation of T lymphocytes (Paper V). Our preliminary data indicate increased production of both pro inflammatory and antiinflammatory cytokines by peripheral blood T cells in the presence of soluble factors from the inflamed colonic mucosa of CC patients compared to controls.

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2013. p. 83
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 84
Keywords
Microscopic colitis, collagenous colitis, lymphocytic colitis, intraepithelial lymphocytes, lamina propria lymphocytes, T cell receptor excision circle, T helper cells, cytotoxic T lymphocyte and mucosal cytokines
National Category
Medical and Health Sciences
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-27894 (URN)978-91-7668-929-5 (ISBN)
Public defence
2013-05-24, Hörsal P2, Prismahuset, Örebro universitet, Fakultetsgatan 1, Örebro, 09:00 (Swedish)
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Available from: 2013-03-18 Created: 2013-03-11 Last updated: 2019-03-26Bibliographically approved

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Kumawat, Ashok KumarStrid, HiljaElgbratt, KristinaTysk, CurtBohr, JohanHultgren Hörnquist, Elisabeth

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Kumawat, Ashok KumarStrid, HiljaElgbratt, KristinaTysk, CurtBohr, JohanHultgren Hörnquist, Elisabeth
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School of Health and Medical Sciences, Örebro University, SwedenÖrebro University HospitalSchool of Medicine, Örebro University, Sweden
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Medical and Health SciencesGastroenterology and Hepatology

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