IL-10 MEDIATES IMMUNOSUPPRESSION FOLLOWING PRIMARY INFECTION WITH TOXOPLASMA-GONDII IN MICE

Suppression of the host immune response by Toxoplasma gondii has been observed in both human and experimental murine infection. In this stud y, inbred mice were infected with T. gondii. At day 7 post-infection, the lymphoproliferative response to both mitogen and superantigen as w ell as parasite antigen were found to be significantly depressed. Usin g a transwell system, it was determined that the reduced proliferative response was due to soluble factor(s) being expressed by splenocytes from the infected mice. Isolation of the splenocytes into an adherent and nonadherent population suggested that both macrophages and T cells were able to produce at least one soluble factor. Tissue culture supe rnatant derived from the splenocytes of the infected mice contain incr eased levels of IL-10, whereas measurable IL-2 levels could not be qua ntitated. At day 7 post-infection, both a biologic assay for IFN-gamma in culture supernatant and the expression of IFN-gamma mRNA in the sp lenocytes were reduced. Antibody to IL-IO was able to partially neutra lize (almost 50%) the in vitro immune downregulation of the tissue cul ture supernatant. Anti-IL-10 in combination with a nitric oxide (NO) a ntagonist was able to reverse the inhibitory activity of the culture s upernatant by 85%. Since IL-10 is a potent antagonist of IFN-gamma, it may represent a critical cytokine involved in mediating T. gondii ind uced immunosuppression in the infected host.