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Cytomegalovirus (CMV) establishes a life-long, persistent/latent infection. Continuous immune surveillance by CMV-specific CD8+ T cells results in their accumulation over time, a process called “memory inflation”. These “inflationary” T cells migrate systemically and comprise the largest T cell populations in humans, making CMV-based vaccines attractive. Why T cells specific for only some CMV-derived epitopes undergo inflation is unclear. We found previously that recombinant murine (M)CMV expressing the SIINFEKL peptide only induced inflation of SIINFEKL-specific T cells, in contrast to wild-type MCMV infection. We show here that:

  • Co-infecting mice with viruses expressing and lacking SIINFEKL enabled T cells with multiple specificities to inflate.
  • Adoptively transferred OT-I T cells, which have a high affinity for the SIINFEKL peptide, were preferentially enriched shortly after infection.
  • Adoptively transferred OT-I T cells inhibited the inflation of host-derived T cells specific for SIINFEKL.
  • We observed sporadic, late rejection of OT-Is as a result of minor histocompatibility differences between donor and recipients. Only such rejection enabled host-derived T cells to inflate robustly.