CD8(+) T-cell priming against a nonsecreted Listeria monocytogenes antigenis independent of the antimicrobial activities of gamma interferon

Sublethal infection of mice with recombinant Listeria monocytogenes express ing a model epitope in either secreted or nonsecreted form results in simil ar CD8(+) T-cell priming. Since nonsecreted bacterial proteins have no obvi ous access to the endogenous major histocompatibility complex (MHC) class I presentation pathway, presentation of these antigens requires destruction of the bacterium to reveal the nonsecreted molecules to an exogenous MHC cl ass I presentation pathway. Gamma interferon (IFN-gamma), a cytokine made b y multiple cell types in response to L. monocytogenes infection, could be r equired for exogenous presentation of nonsecreted bacterial antigens via it s capacity to upregulate the expression of molecules involved in antigen pr esentation, its capacity to activate macrophages to kill bacteria to expose nonsecreted molecules or both. IFN-gamma knockout (KO) mice were used to a ddress the requirement for IFN-gamma in CD8(+) T-cell priming against (i) a model exogenous antigen and (ii) secreted and nonsecreted L. monocytogenes antigens. We demonstrate that IFN-gamma KO mice are capable of cross-prese nting the model exogenous antigen ovalbumin to prime CD8(+) T-cell response s that are only slightly weaker than that in wild-type (WT) mice. Despite t heir extreme susceptibility to primary L. monocytogenes infection, previous ly immunized and naive IFN-gamma KO mice were able to generate CD8(+) T-cel l responses against both secreted and nonsecreted L. monocytogenes antigens which were similar to responses of WT mice. Interestingly, IFN-gamma KO mi te were as capable as WT mice in mediating the characteristic drop in bacte rial load in the liver at 4 h postinfection, although the IFN-gamma KO mice have exacerbated bacterial loads as early as 24 h postinfection. These res ults demonstrate that the regulatory functions of IFN-gamma are not require d for priming of CD8(+) T cells by cross-presentation of a model exogenous antigen or in response to a nonsecreted L. monocytogenes antigen. In additi on, the capacity of IFN-gamma to activate the microbicidal activities of ma crophages is not required for the very early innate immune response to L. m onocytogenes or priming of CD8(+) T cells against a nonsecreted bacterial a ntigen.