Trypanosoma cruzi: predominance of IgG2a in nonspecific humoral response during experimental Chagas' disease.

The kinetic and isotypic pattern of hypergammaglobulinemia has been investigated in C3H/HeJ infected with Trypanosoma cruzi. Hypergammaglobulinemia appeared 14 days postinfection, increased until Day 28 postinfection, and persisted throughout the chronic phase (greater than 60 days of infection). The main isotype secreted was IgG2a, reaching 10-fold the control level. High titers of autoantibodies were found of IgM and IgG subclasses. Isotypic characterization of antibodies against myosin, myelin, and keratin, was performed and determined to be IgG2a subclass in the chronic stage of infection. Specific responses against T. cruzi took place 2 weeks postinfection when the parasitemia was high. Interestingly, parasite-specific response was maximal after 4 weeks of infection and plateaued during the chronic phase when parasites were rare. In contrast to the humoral polyclonal response in the chronic stage, showing a preferential IgG2a pattern, the anti-T. cruzi response consisted of all the different isotypes: IgM, IgG1, IgG3, IgG2a, and IgG2b, throughout the infection. Identical patterns of parasite antigens were recognized by IgG2a and IgG2b antibodies. Few different antigens were identified by the IgG3. Some antigens were recognized by several isotypes, others by only one isotype. With regard to the existence of antigenic cross-reactivities between host and parasite, we designed absorption experiments on parasite-specific immunoadsorbent showing that specific antibodies eluted from the column failed to recognize the natural antigens. These studies suggest that nonspecific and antiparasite-specific responses may be maintained by different regulatory pathways.