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Publication : Deficient anti-listerial immunity in the absence of perforin can be restored by increasing memory CD8+ T cell numbers.

First Author  Messingham KA Year  2003
Journal  J Immunol Volume  171
Issue  8 Pages  4254-62
PubMed ID  14530349 Mgi Jnum  J:120042
Mgi Id  MGI:3703721 Doi  10.4049/jimmunol.171.8.4254
Citation  Messingham KA, et al. (2003) Deficient anti-listerial immunity in the absence of perforin can be restored by increasing memory CD8+ T cell numbers. J Immunol 171(8):4254-62
abstractText  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 approximately 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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