Role of CD28 for the generation and expansion of antigen-specific CD8(+) Tlymphocytes during infection with Listeria monocytogenes

\Infection of mice with the intracellular bacterium Listeria monocytogenes results in a strong CD8(+) T cell response that is critical for efficient c ontrol of infection. We used CD28-deficient mice to characterize the functi on of CD28 during Listeria infection, with a main emphasis on Listeria-spec ific CD8(+) T cells. Frequencies and effector functions of these T cells we re determined using MHC class I tetramers, single cell IFN-gamma production and Listeria-specific cytotoxicity. During primary Listeria infection of C D28(-/-) mice. we observed significantly reduced numbers of Listeria-specif ic CD8(+) T cells and only marginal levels of specific IFN-gamma production and cytotoxicity. Although frequencies were also reduced in CD28(-/-) mice during secondary response, we detected a considerable population of Lister ia-specific CD8(+) T cells in these mice. In parallel, IFN-gamma production and cytotoxicity were observed, revealing that Listeria-specific CD8(+) T cells in CD28(-/-) mice expressed normal effector functions. Consistent wit h their impaired CD8(+) T cell activation, CD28(-/-) mice suffered from exa cerbated listeriosis both after primary and secondary infection. These resu lts demonstrate participation of CD28 signaling in the generation and expan sion of Ag-specific CD8(+) T cells in listeriosis. However, Ag-specific CD8 (+) T cells generated in the absence of CD28 differentiated into normal eff ector and memory T cells.