Listeria monocytogenes infection overcomes the requirement for CD40 ligandin exogenous antigen presentation to CD8(+) T cells

In vivo priming of CD8(+) T lymphocytes against exogenously processed model Ags requires CD4(+) T cell help, specifically interactions between CD40 li gand (CD40L) expressed by activated CD4(+) T cells and CD40, which is prese nt on professional APC such as dendritic cells (DCs). To address this issue in the context of bacterial infection, we examined CD40L-CD40 interactions in CD8(+) T cell priming against an exogenously processed, nonsecreted bac terial Ag. CD40L interactions were blocked by in vivo treatment with anti-C D40L mAb MR-1, which inhibited germinal center formation and CD8(+) T cell cross-priming against an exogenous model Ag, OVA. In contrast, MR-1 treatme nt did not interfere with CD8(+) T cell priming against a nonsecreted or se creted recombinant Ag expressed by Listeria monocytogenes. Memory and secon dary responses of CD8(+) T cells against nonsecreted and secreted bacterial Ags were also largely unimpaired by transient MR-1 treatment. When MR-1-tr eated mice were concurrently immunized with L monocytogenes and OVA-loaded splenocytes, cross-priming of OVA-specific naive CD8+ T cells occurred. No significant decline in cross-priming against OVA was measured when either T NF or IFN-gamma was neutralized in L monocytogenes-infected animals, demons trating that multiple signals exist to overcome CD40L blockade of CD8(+) T cell cross-priming during bacterial infection. These data support a model i n which DCs can be stimulated in vivo through signals other than CD40, beco ming APC that can effectively stimulate CD8(+) T cell responses against exo genous Ags during infection.