INHIBITION OF TRYPANOSOMA-CRUZI-SPECIFIC IMMUNE-RESPONSES BY A PROTEIN PRODUCED BY TRYPANOSOMA-CRUZI IN THE COURSE OF CHAGAS-DISEASE

Immunosuppression is readily demonstrable in the acute phase of Trypan osoma cruzi infection but subsides during the ch tonic phase. In vitro , living T. cruzi induces important alterations in mitogen-activated h uman T and B lymphocytes and inhibits their capacity to proliferate. T hese effects are reproduced by a protein spontaneously released by thi s parasite, termed trypanosomal immunosuppressive factor (TIF). In thi s study we asked whether TIF would also inhibit a T. cruzi-specific im mune response and if it is produced in a mammalian host during infecti on. A significant reduction in the level of [H-3]thymidine incorporati on by spleen cells from chronically infected mice stimulated with a T. cruzi antigen preparation ensued when TIF was added to the cultures. Production of TIF in T. cruzi-infected individuals was denoted by the ability of serum IgG from either chronically infected patients or mice to abolish, in a concentration-dependent manner, the capacity of TIF to suppress interleukin-2 receptor expression by phytohaemagglutinin-s timulated human lymphocytes. This neutralizing activity was absent in the IgG fractions prepared from sera of healthy volunteers, noninfecte d mice or mice killed at different times during acute T. cruzi infecti on. Circulating anti-TIF antibodies represent indirect evidence of TIF production in vivo which, together with TIF-mediated inhibition of T. cruzi-specific lymphoproliferation, raise the possibility that TIF co ntrols antiparasite immune responses in vivo. The presence of TIF-neut ralizing antibodies during chronic but not acute T. cruzi infection ma y be one of the reasons why immunosuppression is confined to the acute stage.