Alteration of intestinal intraepithelial lymphocytes after massive small bowel resection

Intraepithelial lymphocytes (IEL) comprise the inner most layer of the gut immune system, and play a critical role in protecting the host from enteric organisms. Massive small bowel resection (MSBR) is one such clinical condition where patients are at particularly high risk for the development of such enteric infectious complications. Because of this, we hypothesized that the IEL may change significantly after the formation of a MSBR. To address this, a mouse model of MSBR was created and the acute phenotypic and functional characteristics of the IEL were studied.

Mice underwent a 70% mid-small bowel resection. After 7 days, IEL were isolated and analyzed for phenotypic changes by flow cytometry. IEL cytokine expression was performed with semiquantitative polymerase chain reaction techniques. To assess the functional significance of these changes, IEL proliferative response was assessed in vitro.Results. MSBR led to significant decreases in specific IEL subpopulations: CD 44+ (used as a marker of cell maturity); CD 8alphabeta+ (marker of thymic derivation), and CD 69+ (marker of T cell activation). Compared with controls, IEL TNF-alpha mRNA expression increased 84%, while IL-2 and IL-10 mRNA expression decreased by 69 and 72%, respectively. Spontaneous proliferation of IEL in the MSBR group was significantly higher than controls, however, proliferation failed to increase with T cell stimulation.Conclusion. These changes suggest a shift to a more immature and possibly less activated cell population. It is possible that such alterations may play an important role in the increase in enterically derived infections in patients with MSBR.