Batf3 transcription factor-dependent DC subsets in murine CMV infection: Differential impact on T-cell priming and memory inflation

Priming of CD8 ⁺ T cells specific for viruses that interfere with the MHC class I presentation pathway is a challenge for the immune system and is believed to rely on cross-presentation. Cytomegalovirus (CMV) infection induces vigorous CD8 ⁺ T-cell responses despite its potent immune evasion strategies. Furthermore, CD8 ⁺ T cells specific for a subset of viral epitopes accumulate and are maintained at high levels exhibiting an activated phenotype - referred to as "inflationary T cells". Taking advantage Batf3 ^-/- mice in which the development of cross-presenting CD8α ⁺ and CD103 ⁺ DCs is severely compromised, we analyzed their role in the induction and inflation of murine (M)CMV-specific CD8 ⁺ T-cell responses. We found that priming of MCMV-specific CD8 ⁺ T cells was severely impaired in the absence of cross-presenting DCs. However, inflation of two immuno-dominant MCMV-specific CD8 ⁺ T-cell populations was largely normal in the absence of cross-presenting DCs, indicating that inflation during latency was mainly dependent on direct antigen presentation. These results highlight differential antigen presentation requirements during acute and latent MCMV infection.