Perforin pathway is essential for protection of mice against lethal ocularHSV-1 challenge but not corneal scarring

Perforin (cytolysin; pore-forming protein) is expressed in both CD8(+) cyto toxic T lymphocytes (CTLs) and natural killer (NK) cells, and is a major fa ctor responsible for the cytolytic activities of these cells. Both CD8(+) T -cells and NK cells are important in eliminating cells infected with certai n viruses. We examined the role of perforin in a mouse model of HSV-1 infec tion using perforin-deficient mice. Naive perforin knockout (perforin(o/o)) mice were more susceptible to lethal HSV-1 ocular challenge (60% survival) , than naive parental C57BL/6 (100% survival). In contrast. both C57BL/6 an d perforin(o/o) mice had similar levels of HSV-1 induced corneal scarring. Vaccination of perforin(o/o) mice induced a significantly higher HSV-1 neut ralizing antibody titer than vaccination of C57BL/6 mice, and the mice were completely protected against lethal ocular challenge. These results sugges t that in naive mice ocularly challenged with HSV-1, the perforin pathway w as involved in protection against death, but not in protection against corn eal scarring. (C) 1999 Elsevier Science B.V. All rights reserved.