CD8(-CELL-MEDIATED PROTECTION AGAINST AN INTRACELLULAR BACTERIUM BY PERFORIN-DEPENDENT CYTOTOXICITY() T)

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-d eficient mice generated by homologous recombination. The absence of pe rforin-mediated cytotoxicity resulted in delayed clearance of Listeria from the spleen but not the liver after primary infection, overall su sceptibility 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-deficien t 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. T hese results indicate that the protective effect of CD8(+) T cells aga inst 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.