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 language | English |
---|---|
Pages (from-to) | 927-939 |
Number of pages | 13 |
Journal | International Immunology |
Volume | 22 |
Issue number | 12 |
DOIs | |
Publication status | Published - Dec 2010 |
Externally published | Yes |
Keywords
- Adaptive immune system
- Animal models
- Cytokines
- Inflammation
- Inflammatory bowel disease
- Intraepithelial lymphocytes
- TCRbxδ-deficient mice
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology