INFLUENCE OF BETA(2)-MICROGLOBULIN EXPRESSION ON GAMMA-INTERFERON SECRETION AND TARGET-CELL LYSIS BY INTRAEPITHELIAL LYMPHOCYTES DURING INTESTINAL LISTERIA-MONOCYTOGENES INFECTION

Numerous microbial pathogens, including Listeria monocytogenes, enter the host through the intestine, Although relatively little is known ab out the biological functions of intestinal intraepithelial lymphocytes (i-IEL), they are generally considered a first line of defense agains t intestinal infections, In the mouse, the vast majority of i-IEL expr ess the CD8 coreceptor either as a CD8 alpha/beta homodimer or as a CD 8 alpha/beta heterodimer. The CD8 coreceptor of T-cell receptor (TcR)g amma/delta i-IEL is exclusively homodimeric, whereas the CD8-expressin g TcR alpha/beta i-IEL segregate into equal fractions of CD8 alpha/alp ha and CD8 alpha/beta cells. We infected beta(2)-microglobulin (beta 2 m)(+/-) mice (possessing all i-IEL populations) and beta 2m(-/-) mutan t mice (lacking all CD8 alpha/beta(+) i-IEL and having few CD8 alpha/a lpha(+) TcR alpha/beta i-IEL) with L. monocytogenes per os and determi ned their biological functions after TcR ligation with monoclonal anti bodies, Cytolytic activities of TcR alpha/beta and TcR gamma/delta i-I EL from beta 2m/mice(+/-) were not influenced by intestinal listeriosi s, Cytolytic activities of TcR alpha/beta i-IEL were impaired in uninf ected beta 2m(-/-) mice, but this reduction was reestablished as a con sequence of intestinal listeriosis, Frequencies of gamma interferon (I FN-gamma)-producing TcR alpha/beta i-IEL in uninfected beta 2m(-/-) mi ce were reduced, compared with that in their heterozygous controls, Eq ually low frequencies of IFN-gamma-producing TcR gamma/delta i-IEL in beta 2m(+/-) and beta 2m(-/-) mutants were found. Listeriosis increase d frequencies of IFN-gamma-producing TcR alpha/beta and TcR gamma/delt a i-IEL in both mouse strains, Most remarkably, the proportion of IFN- gamma-producing TcR gamma/delta i-IEL was elevated 10-fold in listeria -infected beta 2m-/- mice. Our findings show that the beta 2m-independ ent CD8 beta(-) i-IEL expressing either TcR alpha/beta or TcR gamma/de lta are stimulated by intestinal listeriosis independent of regional b eta 2m expression, We conclude that the three major CD8(+) i-IEL popul ations are stimulated by intestinal listeriosis and that CD8 beta(-) i -IEL compensate for the total lack of CD8 beta(+) i-IEL in beta 2m(-/- ) mutant mice. Hence, in contrast to the peripheral immune system, whi ch crucially depends on CD8 alpha/beta(+) TcR alpha/beta lymphocytes, the mucosal immune system can rely on additional lymphocytes expressin g the CD8 alpha/alpha homodimer.