Conventional alpha beta T cells are sufficient for innate and adaptive immunity against enteric Listeria monocytogenes

We have begun to dissect the cellular requirements for generation of immuni ty against enteric infection by Listeria monocytogenes using a novel T-B-NK - mouse strain (mice double deficient for the common cytokine receptor gamm a -chain (gamma (c)) and the recombinase-activating gene-2 (RAG2/gamma (c) mice). Initial experiments showed that C57BL/6 mice and alymphoid RAG2/gamm a (c), mice had similar kinetics of bacterial accumulation in the spleen, l iver, and brain early after intragastric L. monocytogenes infection (up to day 3), calling into question the physiologic role of gut-associated lympho id cells during the passage of this enterobacterium into the host. However, in contrast to C57BL/6 mice, RAG2/y(c), mice rapidly succumbed to dissemin ated infection by day 7. Polyclonal lymph node CD4(+) and CD8(+) alpha beta T cells were able to confer RAG2/gamma (c) mice with long-lasting protecti on against enteric L. monocytogenes infection in the absence of gamma delta T, NK, and NK-T cells. Moreover, these alpha beta T-reconstituted RAG2/gam ma (c) mice produced IFN-gamma at levels comparable to C57BL/6 mice in resp onse to L. monocytogenes both in vitro and in vivo. Protection was IFN-gamm a dependent, as RAG2/gamma (c) mice reconstituted with IFN-gamma -deficient alpha beta T cells were unable to control enteric L. monocytogenes infecti on. Furthermore, alpha beta T cell-reconstituted RAG2/gamma (c) mice were a ble to mount memory responses when challenged with lethal doses of L. monoc ytogenes. These data suggest that NK, NK-T, gamma delta T, and B cells are functionally redundant in the immunity against oral L. monocytogenes infect ion, and that in their absence alpha beta T cells are able to mediate the e arly IFN-gamma production required for both innate and adaptive immunity.