Evaluation of the immunoregulatory activity of intraepithelial lymphocytes in a mouse model of chronic intestinal inflammation

D. V. Ostanin, C. M. Brown, L. Gray, S. Bharwani, M. B. Grisham

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Intraepithelial lymphocytes (IELs) represent the first line of lymphocyte defense against the intestinal bacteria. Although previous studies have demonstrated a protective role of IELs in the development of colitis, the data supporting a regulatory role for IELs are limited. The objective of this study was to examine the suppressive activity of IELs in vitro and in vivo using a mouse model of chronic small and large bowel inflammation. Adoptive transfer of CD8α+ IELs isolated from small intestines of wildtype (WT) mice into TCR βxδ-deficient (TCR βxδ-/-) recipients did not prevent or delay the onset of the disease induced by WT CD4+CD45RBhigh T cells. On the contrary, we observed a more rapid onset of wasting and clinical signs of intestinal inflammation when compared with animals injected with CD4+CD45RBhigh T cells alone. Histopathological scores of small and large bowel did not differ significantly between the two groups. Transfer of IELs alone did not produce any pathological changes. Real-time PCR analysis of intestinal tissues showed up-regulation of message for Th1- and macrophage-derived cytokines in colon and small bowel. Using Foxp3-GFP reporter mice, we were unable to detect any Foxp3+ cells within the CD8α+ IELs but did find a small population of Foxp3+CD4+ IELs in the small and large bowel. Using in vitro suppression assay, we found that neither TCRαβ+CD8αα+, TCRαβ+CD8αβ+ nor TCRγδ+CD8αα+ IELs were capable of suppressing CD4+ T-cell proliferation. Taken together, our data do not support an immunoregulatory role for CD8α+ IELs in a mouse model of small and large bowel inflammation.

Original languageEnglish
Pages (from-to)927-939
Number of pages13
JournalInternational Immunology
Volume22
Issue number12
DOIs
Publication statusPublished - Dec 2010

Keywords

  • Adaptive immune system
  • Animal models
  • Cytokines
  • Inflammation
  • Inflammatory bowel disease
  • Intraepithelial lymphocytes
  • TCRbxδ-deficient mice

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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