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 (Kb-/-D b-/- M3-/-). The CD8+ T cells present in Kb-/-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 Kb-/-D b-/-M3-/- mice compared with that in Kb-/-D b-/- mice, this population retains the capacity to expand significantly in response to primary infection with the bacteria Listeria monocytogenes. However, Kb-/-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 Kb-/-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 Kb-/-D b-/-M3 -/- mice exhibit reduced bacterial burden compared with that of infected β2-microglobulin-deficient mice that lack MHC class Ib-restricted CD8+ T cells altogether. In addition, adoptive transfer of Listeria-experienced Kb-/-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.
ASJC Scopus subject areas
- Immunology and Allergy