Regulation of CD8⁺ T cells undergoing primary and secondary responses to infection in the same host

Naive Ag-specific CD8⁺ T cells expand, contract, and become memory cells after infection and/or vaccination. Memory CD8⁺ T cells provide faster, more effective secondary responses against repeated exposure to the same pathogen. Using an adoptive transfer system with low numbers of trackable nontransgenic memory CD8⁺ T cells, we showed that secondary responses can be comprised of both primary (naive) and secondary (memory) CD8⁺ T cells after bacterial (Listeria monocytogenes) and/or viral (lymphocytic choriomeningitis virus) infections. The level of memory CD8⁺ T cells present at the time of infection inversely correlated with the magnitude of primary CD8⁺ T cell responses against the same epitope but directly correlated with the level of protection against infection. However, similar numbers of Ag-specific CD8⁺ T cells were found 8 days postinfection no matter how many memory cells were present at the time of infection. Rapid contraction of primary CD8⁺ T cell responses was not influenced by the presence of memory CD8⁺ T cells. However, contraction of secondary CD8⁺ T cell responses was markedly prolonged compared with primary responses in the same host mice. This situation occurred in response to lymphocytic choriomeningitis virus or L. monocytogenes infection and for CD8⁺ T cell responses against multiple epitopes. The delayed contraction of secondary CD8⁺ T cells was also observed after immunization with peptide-coated dendritic cells. Together, the results show that the level of memory CD8⁺ T cells influences protective immunity and activation of naive precursors specific for the same epitope but has little impact on the magnitude or program of the CD8⁺ T cell response.