Secondary CD8+ T-cell responses are controlled by systemic inflammation

Repeated infections and experimental prime-boost regimens frequently result in the generation of secondary (2 degrees) CD8(+) T-cell responses. In contrast to primary (1 degrees) CD8(+) T cells, the parameters that influence the abundance and phenotype of 2 degrees effector and memory CD8(+) T-cell populations are largely unknown. Here, we analyze the impact of different booster infections, Ag curtailment, and systemic inflammation on the quality and quantity of secondary CD8(+) T-cell responses. We show that similar to 1 degrees CD8(+) T-cell responses, the phenotype of 2 degrees effector and memory CD8(+) T-cell populations is critically dependent on the nature of the infectious pathogen and the inflammatory milieu early after infection. In addition, systemic inflammation increases the number of 2 degrees effector and memory CD8(+) T cells after booster infections and immunizations. Therefore, our data reveal new means to boost the number of 2 degrees effector and memory CD8(+) T cells in prime-boost regimens and show a surprisingly high degree of plasticity in 2 degrees memory CD8(+) T-cell phenotype that is controlled by systemic inflammation.