In this study we investigate the attributes of virus-specific memory CD8 T cells which most effectively control
secondary infections. By rechallenging mice that had cleared primary lymphocytic choriomeningitis virus
infections, we revealed that the secondary response is remarkably swift. Within 6 h following
secondary infection, the production of
gamma interferon becomes detectable directly ex vivo. During this protective phase of the secondary response, a very early elaboration of effector activities is preferentially exhibited by T cells specific for the viral NP396
epitope. This wave of activation contains the
infection primarily before the initiation of the proliferative phase of the secondary response. Marked expansion is observed, but its magnitude differs depending on the
epitope specificity of the responding cells; between 42 and 48 h following
infection, approximately 70% of NP396-specific memory cells are in the S phase of the cell cycle, as assessed by
bromodeoxyuridine incorporation studies.
Epitope-dependent differences during the proliferative phase of the secondary response were confirmed by adoptive transfer studies with
CFSE-labeled T cells. Although NP396-specific T cells typically dominate secondary responses, the broader multiepitope-specific population of
antiviral T cells is beneficial for controlling a variant virus with an escape mutation in this
epitope. These findings indicate that the induction and maintenance of a focused response contribute to the clearance of
secondary infections; however, a more diverse pool of
antiviral T cells facilitates long-term immunity to mutable pathogens.