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.

Animal Cytotoxicity, Immunologic CD8-Positive T-Lymphocytes/*IMMUNOLOGY Dose-Response Relationship, Immunologic Immunity, Cellular Immunization, Passive Immunologic Memory Listeria monocytogenes/IMMUNOLOGY Listeria Infections/*IMMUNOLOGY Membrane Glycoproteins/DEFICIENCY/*PHYSIOLOGY Mice Mice, Inbred C57BL Mice, Mutant Strains Support, Non-U.S. Gov't JOURNAL ARTICLE

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