First Author | Ostanin DV | Year | 2010 |
Journal | Int Immunol | Volume | 22 |
Issue | 12 | Pages | 927-39 |
PubMed ID | 21071622 | Mgi Jnum | J:167237 |
Mgi Id | MGI:4867593 | Doi | 10.1093/intimm/dxq447 |
Citation | Ostanin DV, et al. (2010) Evaluation of the immunoregulatory activity of intraepithelial lymphocytes in a mouse model of chronic intestinal inflammation. Int Immunol 22(12):927-39 |
abstractText | 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 CD8alpha(+) IELs isolated from small intestines of wild-type (WT) mice into TCR betaxdelta-deficient (TCR betaxdelta(-/-)) recipients did not prevent or delay the onset of the disease induced by WT CD4(+)CD45RB(high) 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(+)CD45RB(high) 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 T(h)1- and macrophage-derived cytokines in colon and small bowel. Using Foxp3-GFP reporter mice, we were unable to detect any Foxp3(+) cells within the CD8alpha(+) 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 TCRalphabeta(+)CD8alphaalpha(+), TCRalphabeta(+)CD8alphabeta(+) nor TCRgammadelta(+)CD8alphaalpha(+) IELs were capable of suppressing CD4(+) T-cell proliferation. Taken together, our data do not support an immunoregulatory role for CD8alpha(+) IELs in a mouse model of small and large bowel inflammation. |