A TOXOPLASMA GONDII-DERIVED FACTOR(S) STIMULATES IMMUNE DOWN-REGULATION - AN IN-VITRO MODEL

Suppression of the T-cell lymphoproliferative response and downregulat ion of interleukin 2 (IL-2) production by Toxoplasma gondii has been o bserved following in vivo infection. In this study, an experimental in vitro murine system was developed to evaluate the kinetics of these r esponses, Normal. splenocytes from uninfected mice were stimulated wit h either concanavalin A or an anti-CD3 monoclonal antibody and cocultu red with Toxoplasma tachyzoites either directly or separated by a tran swell. A progressive decline in the lymphoproliferative response was o bserved as the concentration of parasites in culture increased, Neithe r heat-killed nor formaldehyde-fixed parasites stimulated this downreg ulatory response by the splenocytes. A decline in IL-2 production was associated with the decrease in lymphocyte proliferation, The addition of an antibody to IL-10 or heat-inactivated anti-Toxoplasma sera to t he culture supernatant partially neutralized the inhibitory effect on lymphocyte proliferation, Cytokine analysis of the responder splenocyt es demonstrated a decrease in the message for IL-2 and IL-2 receptor a nd an increase in IL-10. Together, these observations suggest that dur ing in vitro culture in a murine system, parasite antigens that stimul ate the release of a soluble factor(s), such as IL-10, that inhibits p roliferation of mitogen-stimulated T cells are expressed.