Tissue assessment of colon inflammatory lesions, because of infectious or non-infectious factors, related to patients' immune competence.

Doctoral Dissertation uoadl:2914790 13 Read counter

Faculty of Medicine
Library of the School of Health Sciences
Deposit date:
Antaraki Despoina
Dissertation committee:
Ανδρέας Χ. Λάζαρης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ, Επιβλέπων
Νικόλαος Καβαντζάς, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γεωργία-Ελένη Θωμοπούλου-Λάζαρη, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Γεώργιος Αγρογιάννης, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γεωργία Βρυώνη, Αναπλ. Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Ειρήνη Θυμαρά, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Στρατηγούλα Σακελλαρίου, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Ιστική εκτίμηση φλεγμονωδών αλλοιώσεων παχέος εντέρου, λοιμώδους αιτιοπαθογένεσης ή μη, σε σχέση με την επάρκεια του ανοσιακού συστήματος των ασθενών
Translated title:
Tissue assessment of colon inflammatory lesions, because of infectious or non-infectious factors, related to patients' immune competence.
We attempted to study whether the presence of T-regulatory cells in tissue obtained from patients with an inflammatory bowel disease augment when Cytomegalovirus coexists in the bowel. Experimental data were analysed using statistical methods and were combined with bibliographical references in an attempt to investigate the role of Treg cells in immunodeficient patients with or without CMV infection.
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 coexisted with CMV bowel infection, whereas the second group (control group) consisted of patients with inflammatory bowel disease without CMV infection. Formalin-fixed, paraffin-embedded tissues were immunohistochemically elaborated with CMV-specific and Foxp3 rabbit polyclonal antibodies and the stained sections were microscopically evaluated in order to define Foxp3 protein levels and the attendance of Tregs in specific tissues.
Statistical analysis of the evaluated samples revealed statistically significant correlation between CMV’s presence and high 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 while they were strongly augmented in patients with active IBD. Eosinophils attendance was also examined and the results proved statistically significant correlation between the number of eosinophils and Treg number in the examined samples.
Completing our study a few observations have to be mentioned:
1. Treg number is remarkably higher in patient tissues with acute IBD and serious inflammation. Nevertheless it is unclear whether in vitro Tregs’ suppressive potency that has confirmed as normal in IBD patients, reflect with accuracy their activity in vivo, given the fact that they finally fail to control mucosal inflammation in those patients.
2. The correlation between Foxp3+Tregs and IBD activation could effortlessly be explained by the hypothesis that human immune system tries to overcome the light immune deficiency that led to IBD outbreak and to get protected against it.
3. Treg presence in bowel tissue seems to be protective against CMV and damage it causes and maybe this mechanism is activated without any inconvenience in IBD patients because of their already augmented Treg presence in bowel tissue in an effort to ameliorate the immunoregulatory ability of inflamed tissue.
4. When inflammation is prolonged and certain cells such as eosinophils accumulate, immune system aborts the occupation with the already located tissue inflammation as well as further Treg mobilization, provided that circumstances consolidate.
The findings of our study demonstrate that Treg infiltration in inflamed mucosal tissues of IBD patients show a significant increase when CMV infection coexists in comparison with IBD patients without any intestinal infectious disease. Treg cells play a crucial role in suppressing local inflammation induced by viral intestinal infections and their regulatory potential may improve the state of intestinal mucosa by providing an active defensive mechanism against CMV, even in patients with partial immune deficiency, like IBD patients. The influence of Tregs over viral colon infection of patients with IBD should be further studied retrospectively and prospectively in order to determine whether these Foxp3+ T cells can be of value in a therapeutic context in order to control ongoing inflammation.
Main subject category:
Health Sciences
T regulatory cells, Foxp3, CMV, Inflammatory bowel disease
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