The role of bovine intraepithelial leukocyte-mediated cytotoxicity in enteric antiviral defense.

Godson, D L; Campos, M; Babiuk, L A

The defense of a mucosal surface against viral infection is dependent in part on the leukocyte population resident at that site. In this study, leukocytes from the bovine intestinal epithelium were isolated and assessed for their ability to inhibit in vitro replication of an enteric pathogen, bovine coronavirus (BCV). As well, the intraepithelial leukocytes (IEL) were tested for their ability to mediate different types of cytotoxicity. The IEL were able to inhibit virus replication, and this activity was markedly enhanced by interleukin-2 and tumor necrosis factor. This combination of cytokines has similar effects on IEL-mediated cytotoxicity, which implicated cytotoxicity as a mechanism by which viral replication was limited. The IEL demonstrated enhanced cytotoxic function when compared with lymphocytes isolated from other sites in the gut-associated or systemic immune system. The IEL mediated higher levels of IL-2-activated, antibody-dependent, and lectin-dependent cytotoxicity than did lymphocytes from mesenteric lymph nodes, Peyer's patches, or the spleen. This function may be a reflection of the type of cell recruited to the epithelium, as indicated by the increased prevalence of T cells, and particularly CD8+ cells in the IEL population. Cytokine activation and the presence of a recognition signal, such as antibody, resulted in a synergistic increase in the level of IEL-mediated cytotoxicity. This type of interaction could serve to enhance the efficiency of IEL cytotoxic cells in vivo. Thus IEL-mediated cytotoxicity has the potential to serve as a mechanism of defense to enteric viral infection.