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

Dandamudi, D. B.; Blair, D. A.; Arifa, R.; Lafaille, J. J.; Dustin, M. L.; Mayya, V.

doi:10.1101/456392

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bioRxiv · 10.1101/456392

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

Dandamudi, D. B.·Blair, D. A.·Arifa, R.·Lafaille, J. J.·Dustin, M. L.·Mayya, V.

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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.

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Dandamudi, D. B., Blair, D. A., Arifa, R., Lafaille, J. J., Dustin, M. L., Mayya, V.. 2018-11-02. Multifaceted influence of pre-mitotic cytotoxicity of primed CD8 T cells on immunity and infection. https://doi.org/10.1101/456392

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