Characterization of the memory/activated T cells that mediate the long‐lived host response against tuberculosis after bacillus Calmette–Guérin or DNA vaccination

Abstract

The memory/activated T cells, which mediate the long-lived host response against tuberculosis, in mice immunized with either bacillus Calmette–Guérin (BCG) or mycobacterium heat-shock protein 65 (hsp 65) antigen expressed from plasmid DNA (DNA-hsp 65), were characterized. Protection against Mycobacterium tuberculosis challenge by DNA-hsp 65 vaccination was associated with the presence of lymph node T-cell populations in which CD8⁺/CD44^hi interferon-γ (IFN-γ)-producing/cytotoxic cells were prominent even after 8 or 15 months of plasmid DNA-mediated immunizations, whereas after BCG vaccination the majority were CD4⁺/CD44^lo IFN-γ-producing T cells. When the cells were separated into CD4⁺CD8⁻ and CD8⁺CD4⁻ and then into CD44^hi and CD44^lo types, CD44^lo cells were essentially unable to transfer protection in adoptive transfer experiments, the most protective CD44^hi cells were CD8⁺CD4⁻ and those from DNA-vaccinated mice were much more protective than those from BCG-immunized mice. The frequency of protective T cells and the level of protection were increased up to 8 months and decreased after 15 months following DNA or BCG immunizations.