The function of intestinal intraepithelial T lymphocytes for repair of epithelial barrier during challenge with the coccidial pathogen Eimeria spp.

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IEL that reside at the basolateral site of epithelial cells (EC). We found that IEL express junctional molecules, occludin and E-cadherin EC, suggesting possibility of a novel barrier function of IEL and communication between IEL and EC. Eimeria spp.' are intracellular protozoan parasite that cause coccidiosis. IEL have been suggested to have immunoregulatory and immunoprotective roles against Eimeria spp. infection. To investigate how IEL are involved in the regulation of epithelial barrier during Eimeria spp. infection, we demonstrated two distinct roles of IEL against infection with Eimeria vermiformis (E. vermiformis), a murine pathogen; production of cytokines to induce protective immunity and expression of junctional molecules to preserve epithelial barrier. The number of IEL markedly increased when oocyst W production reached a peak. During infection, IEL increased production of IFN-γ and TNF-α and decreased TGF-β. production. Addition of IFN-γ and TNF-α or supematants obtained from cultured IEL from E. vermiformis-infected mice reduced transepithelial electrical resistance (TER) in confluent CMT93 cell monolayer, a murine intestinal-derived epithelial line, but antibodies against these cytokines suppressed the decline of TER. Moreover, TGF-β attenuates the damage of epithelial monolayer and changes in TER caused by IFN-γ and TNF-α. The expression of junctional molecules by EC was decreased when IEL produced a high level of IFN-γ and TNF-α, and a low level of TGF-β in E. vermiformis-infected mice. Interestingly, IEL constantly expressed junctional molecules and a co-culture of EC with IEL increased TER. These results suggest that IEL play important multi-functional roles not only in protection of the epithelium against E vermiformis-induced change by cytokine production but also direct interaction with the epithelial barrier when intra-EC junctions are down-regulated.