LISTERIA-MONOCYTOGENES-INDUCED GAMMA-INTERFERON SECRETION BY INTESTINAL INTRAEPITHELIAL GAMMA-DELTA T-LYMPHOCYTES

Gamma/delta T cells represent a major proportion of intestinal intraep ithelial lymphocytes (IEL), and it has been suggested that these IEL s erve as a first immune barrier against microbial invasion and that the y do so by destroying infected epithelial cells. In the present study, we confirm that both alpha/beta and gamma/delta IEL from naive mice e xpress potent cytotoxicity and produce gamma interferon (IFN-gamma) af ter T-cell receptor (TCR) engagement by specific monoclonal antibodies (MAb). Intraperitoneal administration of the anti-gamma/delta TCR MAb GL3 caused downregulation of the gamma/delta TCR in IEL, and IEL from gamma/delta TCR-modulated mice failed to express cytotoxic activity a nd to secrete IFN-gamma after gamma/delta TCR engagement. In contrast, alpha/beta IEL from such mice were still cytolytic and secreted IFN-g amma. Mice were infected orally with virulent Listeria monocytogenes a t doses which caused bacterial invasion through the intestinal epithel ia. Although alpha/beta and gamma/delta IEL from these mice expressed high cytolytic activities in antibody-redirected killer assays, target cells pulsed with listerial antigens were not lysed. In contrast, IFN -gamma secretion by IEL from L. monocytogenes-infected mice was induce d not only by anti-TCR MAb but also by target cells pulsed with lister ial antigens, whereas irrelevant antigens, including heat shock protei n 60, did not induce IFN-gamma secretion. Furthermore, the number of I FN-gamma-secreting IEL, as assessed by the enzyme-linked immunospot te chnique, was increased during listeriosis. Gamma/delta TCR modulation by GL3 administration abrogated antigen-induced IFN-gamma secretion by IEL from infected mice. These findings suggest that L. monocytogenes induced IFN-gamma secretion by gamma/delta IEL from mice suffering fro m intestinal L. monocytogenes infection and invasion. Thus, the data p rovide evidence for a role of IFN-gamma-secreting IEL in local resista nce against listeriosis and perhaps other food-borne diseases.