Nonconventional CD8+ T Cell Responses to Listeria Infection in Mice Lacking MHC Class Ia and H2-M3

CD8 + T cells restricted to MHC class Ib molecules other than H2-M3 have been shown to recognize bacterial Ags. However, the contribution of these T cells to immune responses against bacterial infection is not well defined. To investigate the immune potential of MHC class Ib-restricted CD8 + T cells, we have generated mice that lack both MHC class Ia and H2-M3 molecules (K b−/− D b−/− M3 −/− ). The CD8 + T cells present in K b−/− D b−/− M3 −/− mice display an activated surface phenotype and are able to secrete IFN-γ rapidly upon anti-CD3 and anti-CD28 stimulation. Although the CD8 + T cell population is reduced in K b−/− D b−/− M3 −/− mice compared with that in K b−/− D b−/− mice, this population retains the capacity to expand significantly in response to primary infection with the bacteria Listeria monocytogenes . However, K b−/− D b−/− M3 −/− CD8 + T cells do not expand upon secondary infection, similar to what has been observed for H2-M3–restricted T cells. CD8 + T cells isolated from Listeria -infected K b−/− D b−/− M3 −/− mice exhibit cytotoxicity and secrete proinflammatory cytokines in response to Listeria -infected APCs. These T cells are protective against primary Listeria infection, as Listeria -infected K b−/− D b−/− M3 −/− mice exhibit reduced bacterial burden compared with that of infected β 2 -microglobulin–deficient mice that lack MHC class Ib-restricted CD8 + T cells altogether. In addition, adoptive transfer of Listeria -experienced K b−/− D b−/− M3 −/− splenocytes protects recipient mice against subsequent Listeria infection in a CD8 + T cell-dependent manner. These data demonstrate that other MHC class Ib-restricted CD8 + T cells, in addition to H2-M3–restricted T cells, contribute to antilisterial immunity and may contribute to immune responses against other intracellular bacteria.