In vivo modulation of T cell responses and protective immunity by TCR antagonism during infection.

Infectious agents are known to express altered peptide ligands that antagonize T cells in vitro; however, direct evidence of TCR antagonism during infection is still lacking, and its importance in the context of infection remains to be established. In this study, we used a murine model of infection with recombinant Listeria monocytogenes and addressed three issues that are critical for assessing the role of TCR antagonism in the modulation of the immune response. First, we demonstrated that the antagonist peptide efficiently inhibited the ability of the agonist to prime naive TCR-transgenic T cells in vivo.

Activation of antigen-specific CD8 T cells results in minimal killing of bystander bacteria.

Memory CD8 T cells play a critical role in protective immunity against intracellular pathogens. In addition to their ability to specifically recognize and lyse infected targets, activated CD8 T cells secrete cytokines that induce phagocytic cells to engulf and kill bacterial pathogens. In this study, we asked whether activation of Ag-specific CD8 T cells results in nonspecific killing of bystander bacteria during a mixed infection.

Selective depletion of nonspecific T cells during the early stage of immune responses to infection.

Transient T cell depletion occurs before the development of an effective immune response to infection. In this study we show that most T cells, regardless of specificity, are induced to express early activation markers soon after infection with Listeria monocytogenes or lymphocytic choriomeningitis virus. Ag-specific T cells are further activated to display late activation markers and undergo extensive proliferation.