Enhancement of the Listeria monocytogenes p60-specific CD4 and CD8 T cell memory by nonpathogenic Listeria innocua

The contact of T cells to cross-reactive antigenic determinants expressed b y nonpathogenic environmental micro-organisms may contribute to the inducti on or maintenance of T cell memory, This hypothesis was evaluated in the mo del of murine Listeria monocytogenes infection. The influence of nonpathoge nic L. innocua on the L, monocytogenes p60-specific T cell response was ana lyzed. Ne show that some CD4 T cell clones raised against purified p60 from L. monocytogenes cross-react with p60 purified from L, innocua, The L. mon ocytogenes p60-specific CD4 T cell clone 1A recognized the corresponding L. innocua p60 peptide QAAKPAPAPSTN, which differs only in the first amino ac id residue. In vitro experiments revealed that after L. monocytogenes infec tion of APCs, MHC class I-restricted presentation of p60 occurs, while MHC class II-restricted p60 presentation is inhibited. L, innocua-infected cell s presented p60 more weakly but equally well in the context of both MHC cla ss I and MHC class II. In contrast to these in vitro experiments the infect ion of mice with L, monocytogenes induced a strong p60-specific CD4 and CD8 T cell response, while L, innocua infection failed to induce p60-specific T cells, L, innocua booster infection, however, expanded p60-specific memor y T cells induced by previous L, monocytogenes infection. In conclusion, th ese findings suggest that infection with a frequently occurring environment al bacterium such as L, innocua, which is nonpathogenic and not adapted to intracellular replication, can contribute to the maintenance of memory T ce lls specific for a related intracellular pathogen.