Interleukin-12 restores dendritic cell function and cell-mediated immunity in retrovirus-infected mice.
The effects of IL-12 treatment on the defects in DC function and on the reduced cell-mediated immunity induced in mice infected with Rauscher leukemia virus (RLV) were studied. DC from RLV-infected mice failed to stimulate significant allogeneic T cell proliferation but T cells from RLV-infected mice showed normal responses to allogeneic DC. In RLV-infected mice treatment with 5 doses of 100 or 300 ng IL-12 around the time of infection resulted in DC that stimulated normal T cell proliferation. Treatment of mice with 300 ng IL-12 but not 100 ng reduced T cell responses. RLV-infected mice showed reduced delayed hypersensitivity to a contact sensitizer. Infected animals receiving the low dose of IL-12 which allowed normal DC and T cell function gave normal delayed hypersensitivity reactions; IL-12 thus resulted in both normal T cell stimulation by DC and cell-mediated immunity. A failure of T cell stimulation by DC is associated with immunosuppression in retrovirus infection and the enhanced capacity of DC to stimulate T cells after IL-12 treatment may be beneficial.
Williams
N J
NJ
Antigen Presentation Research Group, Imperial College School of Medicine, Northwick Park Institute for Medical Research, Harrow, Middlesex, United Kingdom.
Harvey
J J
JJ
Duncan
I
I
Booth
R F
RF
Knight
S C
SC
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D017209:Apoptosis; D003713:Dendritic Cells / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006968:Hypersensitivity, Delayed; D007111:Immunity, Cellular; D018664:Interleukin-12 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D011925:Rauscher Virus / Q000276:immunology*; D012192:Retroviridae Infections / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000821:virology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D015703:Antigens, CD; D018664:Interleukin-12