Attrition of T Cell Memory: Selective Loss of LCMV Epitope–Specific Memory CD8 T Cells following Infections with Heterologous Viruses

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Using a variety of techniques, including limiting dilution assays (LDA), intracellular IFNγ assays, and D b-IgG1 MHC dimer staining to measure viral peptide-specific T cell number and function, we show here that heterologous virus infections quantitatively delete and qualitatively alter the memory pool of T cells specific to a previously encountered virus. We also show that a prior history of a virus infection can alter the hierarchy of the immunodominant peptide response to a second virus and that virus infections selectively reactivate memory T cells with distinct specificities to earlier viruses. These results are consistent with a model for the immune system that accommodates memory T cell populations for multiple pathogens over the course of a lifetime.