Multifaceted influence of pre-mitotic cytotoxicity of primed CD8 T cells on immunity and infection

Abstract

Granzyme B mRNA is expressed in primed CD8 T cells within 12 hours, but the consequences of this for the immune response are unknown. We observed that substantial portion of the naive CD8 T cell repertoire expressed granzyme B and became pre-mitotic cytotoxic cells (PMCs) immediately in response to Listeria monocytogenes or Lymphocytic choriomeningitis virus infections. The surprising breadth arose from sufficiency of low potency peptide-MHC to induce granzyme B expression in the context of infection. PMCs killed antigen bearing dendritic cells (DCs) in a granzyme B-dependent but largely perforinindependent fashion between 1-2 days post infection. This terminated antigen presentation at 3 days and resulted in reduced clonal expansion. As additional consequences, we highlight that PMCs reduced the burden of DC-borne infectious agents, but also opened a window of vulnerability for secondary infection. Thus, PMCs serve antigen-specific, regulatory and host defence functions, that are innate-like in scale, at the onset of the adaptive immune response.