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/IL-15R beta chain in protective immunity against systemic infection with herpes simplex virus type 2 (HSV-2), IL-2/IL-15 receptor(R)beta knock-out mice were inoculated intraperitoneally with HSV-2 strain 186. IL-2/IL-15R beta-deficient mice were susceptible to systemic HSV-2 infection compared with their heterozygous littermates. 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 cells were normally detected in the peritoneal cavity after infection with HSV-2. However, the generation of HSV-2-specific CD4(+) T helper (Th) 1 cells producing interferon-gamma was impaired in IL-2/IL-15R beta knock-out mice following HSV-2 infection. The serum IL-15 level in control mice was increased in the early stage after HSV-2 infection but was not detectable in IL-2/IL-15R beta knock-out mice. In vivo administration of recombinant IL-15 protected normal mice from HSV-2-induced lethality, accompanied by increases in numbers of NK cells and HSV-2-specific Th1 cells. Taken together, these results suggest that IL-15, using the IL-2/IL15R beta chain, plays an important role in mounting protective immunity during the course of systemic HSV-2 infection.
Tsunobuchi
H
H
Laboratory of Host Defense & Germfree Life, Research Institute for Disease Mechanism & Control, Nagoya, Japan.
Nishimura
H
H
Goshima
F
F
Daikoku
T
T
Suzuki
H
H
Nakashima
I
I
Nishiyama
Y
Y
Yoshikai
Y
Y
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001202:Ascitic Fluid / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D017353:Gene Deletion; D006558:Herpes Genitalis / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D019409:Interleukin-15 / Q000097:blood / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use; D007376:Interleukin-2 / Q000097:blood / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D015996:Survival Rate; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; C508024:IL15RA protein, human; C508025:Il15ra protein, mouse; D019409:Interleukin-15; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma