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 havebeen shown to recognizebacterial Ags. However, the contribution of these T cells to immune responses againstbacterial infection is not well defined. To investigate the immune potential of MHC class Ib-restricted CD8(+) T cells, we have generated mice that lackboth MHC class Ia and H2-M3 molecules (Kb-/- Db-/- M3(-/-)). The CD8(+) T cells present in Kb-/- Db-/- M3(-/-) mice display an activated surface phenotype and are able to secrete IFN-g rapidly upon anti-CD3 and anti-CD28 stimulation. Although the CD8(+) T cell population is reduced in Kb-/- Db-/- M3(-/-) mice compared with that in Kb-/- Db-/- mice, this population retains the capacity to expand significantly in response to primary infection with thebacteria Listeria monocytogenes. However, Kb-/- Db-/- M3(-/-) CD8(+) T cells do not expand upon secondary infection, similar to what hasbeen observed for H2-M3-restricted T cells. CD8(+) T cells isolated from Listeria-infected Kb-/- Db-/- 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 Kb-/- Db-/- M3(-/-) mice exhibit reducedbacterialburden compared with that of infectedb2-microglobulin-deficient mice that lack MHC class Ib-restricted CD8(+) T cells altogether. In addition, adoptive transfer of Listeria-experienced Kb-/- Db-/- 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 intracellularbacteria. The Journal of Immunology, 2011, 186: 489-498.