Modulating numbers and phenotype of CD8+ T cells in secondary immune responses

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Abstract
Prime‐boost regimens are frequently used to increase the number of memory CD8+ T cells and thus the protective capacity of experimental vaccinations; however, it is currently unknown how the frequency and phenotype of primary (1°) memory CD8+ T cells impact the quantity and phenotype of secondary (2°) memory CD8+ T‐cell populations. Here, we show that 2° infections of mice that received different 1° infections and/or immunizations generated similar numbers of 2° effector and memory CD8+ T cells. Remarkably, this result was independent of the numbers and phenotype of 1° memory CD8+ T cells present at the time of rechallenge. However, after adoptive transfer of low numbers of 1° memory CD8+ T cells, a linear correlation between 1° memory CD8+ T‐cell input and 2° memory CD8+ T‐cell numbers was observed. These data suggest that, above a very low threshold, boosting of 1° memory CD8+ T‐cell populations elicits 2° immune responses of similar magnitude. Therefore, our study has important implications for the design of prime‐boost regimens that aim to generate protective CD8+ T‐cell‐mediated immunity.