CD8+ T cell‐mediated protection against an intracellular bacterium by perforin‐dependent cytotoxicity

Abstract

Growth of Listeria monocytogenes is mainly controlled by macrophages, which are activated by specific T cells. A potential role of CD8⁺ T cells by direct lysis of infected cells was investigated in perforin‐deficient mice generated by homologous recombination. The absence of perforin‐mediated cytotoxicity resulted in delayed clearance of Listeria from the spleen but not the liver after primary infection, overall susceptibility to Listeria however was not increased. Protection against a secondary infection was drastically impaired in perforin‐deficient mice. Adoptive transfer of immune spleen cells to recipients revealed that anti‐Listeria protection by CD8⁺ T cells from perforin‐deficient versus normal mice was about 10‐fold reduced in livers and about 100‐fold reduced in the spleen of recipients. CD4⁺ T cells from immune control and perforin‐deficient mice conferred comparable protection. These results indicate that the protective effect of CD8⁺ T cells against an intracellular bacterium mainly evident in secondary infection is mediated by a perforin‐dependent pathway, presumably cytotoxicity, and less by other direct or indirect effector mechanisms.