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.