IMMUNOLOGICAL CONTROL OF TRYPANOSOMA-CRUZI INFECTION AND PATHOGENESISOF CHAGAS-DISEASE

The major goal of studies on immunity to Trypanosoma cruzi is the unde rstanding of immunological mechanisms involved in resistance to this p rotozoan as well as the pathogenesis of Chagas' disease. Different stu dies have defined CD8+ T lymphocytes, IFN-gamma and macrophages as imp ortant elements controlling parasite replication during the acute phas e of infection. In contrast, during the chronic stage of the disease p arasite-specific antibodies that fix complement and lyse the blood fro m trypomastigotes are thought to be the main effector molecules respon sible for maintaining latent infection. In both acute and chronic infe ction with T. cruzi CD4+ Th1 lymphocytes appear to be the main cells r esponsible for induction of protective immunity. The immunological mec hanisms involved in the pathogenesis of Chagas' disease are much more controversial. CD8+ lymphocytes are thought to be the main effector ce lls responsible for cardiac tissue destruction. Although many experime nts suggest the involvement of autoimmunity in the pathogenesis of Cha gas' disease, recent studies both in mice and humans indicate a positi ve association of tissue parasitism, inflammation and severity of path ology induced by T. cruzi. Finally, T. cruzi has emerged as an importa nt opportunistic pathogen in patients infected with HIV and presenting low numbers of CD4+ T lymphocytes. These clinical findings indicate t he essential requirement of CD4+ T-helper cells in mediating resistanc e during chronic Chagas' disease; however, the effector mechanisms tha t control the reactivation of chronic infection in vivo are not comple tely defined.