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Deficient Anti-Listerial Immunity in the Absence of Perforin Can Be Restored by Increasing Memory CD8⁺ T Cell Numbers ¹

Kelly A. Nordyke Messingham^*, Vladimir P. Badovinac^* and John T. Harty^2,*,

^* Department of Microbiology and Interdisciplinary Program in Immunology, University of Iowa, Iowa City, IA 52242

Compared with wild-type (WT) mice, Listeria monocytogenes (LM)-vaccinated perforin-deficient (PKO) mice have elevated levels of CD8⁺ T cell memory, but exhibit reduced levels of protection against virulent LM. In this study, Ag-specific CD8⁺ T cells from LM-vaccinated WT and PKO mice were used in adoptive transfer assays to determine the contribution of perforin-dependent cytolysis in protective immunity to LM. Perforin deficiency resulted in an 5-fold reduction in the per-cell protective capacity of Ag-specific memory CD8⁺ T cells that was not caused by differences in memory cell quality as measured by CD62L/CD27 expression, TCR repertoire use, functional avidity, differences in expansion of Ag-specific cells upon infection, or maintenance of memory levels over time. However, perforin-deficient CD8⁺ T cells exhibited reduced in vivo cytotoxic function compared to WT CD8⁺ T cells. Consistent with the existence of perforin-independent effector pathways, double-vaccinated PKO mice were as resistant to challenge with LM as single-vaccinated WT mice. Thus, increasing the number of memory CD8⁺ T cells can overcome diminished per-cell protective immunity in the absence of perforin.

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