A protective role of interleukin-15 in a mouse model for systemic infection with herpes simplex virus

To define the role of cytokine binding to the IL-2/11-15R beta chain in pro tective immunity against systemic infection with herpes simplex virus type 2 (HSV-2), IL-2/IL-15 receptor(R)beta knock-out mice were inoculated intrap eritoneally with HSV-2 strain 186. IL-2/IL-15R beta-deficient mice were sus ceptible to systemic HSV-P infection compared with their heterozygous litte rmates. The emergence of natural killer (NK) cells was impaired in IL-2/IL- 15R beta knock-out mice, but CD4(+) T cell receptor (TCR) alpha beta(+) T c ells were normally detected in the peritoneal cavity after infection with H SV-2. However, the generation of HSV-2-specific CD4(+) T helper (Th) 1 cell s producing interferon-gamma was impaired in IL-2/11-15R beta knock-out mic e following HSV-2. infection. The serum IL-15 level in control mice was inc reased in the early stage after HSV-2 infection but was not detectable in I L-2/IL-15R beta knock-out mice. in vivo administration of recombinant IL-15 protected normal mice from HSV-P-induced lethality, accompanied by increas es in numbers of NK cells and HSV-2-specific Th1 cells. Taken together, the se results suggest that IL-15, using the IL-2/IL15R beta chain, plays an im portant role in mounting protective immunity during the course of systemic HSV-2 infection. (C) 2000 Academic Press.