Interrupting CD28 costimulation before antigen re-challenge affects CD8+ T-cell expansion and effector functions during secondary response in mice

The role of CD28-mediated costimulation in secondary CD8⁺ T-cell responses remains controversial. Here we have used two tools – blocking mouse anti-mouse CD28-specific antibodies and inducible CD28-deleting mice – to obtain definitive answers in mice infected with ovalbumin-secreting Listeria monocytogenes. We report that both blockade and global deletion of CD28 reveal its requirement for full clonal expansion and effector functions such as degranulation and IFN-γ production during the secondary immune response. In contrast, cell-intrinsic deletion of CD28 in transferred TCR-transgenic CD8⁺ T cells before primary infection leads to impaired clonal expansion but an increase in cells able to express effector functions in both primary and secondary responses. We suggest that the proliferation-impaired CD8⁺ T cells respond to CD28-dependent help from their environment by enhanced functional differentiation. Finally, we report that cell-intrinsic deletion of CD28 after the peak of the primary response does not affect the establishment, maintenance, or recall of long-term memory. Thus, if given sufficient time, the progeny of primed CD8⁺ T cells adapt to the absence of this costimulator.

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