A 24000 MW TRYPANOSOMA-CRUZI ANTIGEN IS A B-CELL ACTIVATOR

Trypanosoma cruzi, the causative agent of Chagas' disease, is a protoz oan parasite that infects humans and other mammals in Central and Lati n America. Several alterations of the immune response after infection have been described, such as severe immunosuppression of both cellular and humoral responses and massive polyclonal B- and T-cell activation , including the expansion of self-reactive clones. We have investigate d the effects of the intraperitoneal injection of a recombinant 24 000 MW T. cruzi-specific antigen (rTc24) on the immune response of normal and deficient strains of mice. We analysed the in vivo and ex vivo le vels of lymphocyte activation and the proliferative responses to rTc24 by determining the expression of CD69 activation marker and the level s of thymidine incorporation by spleen cells. The numbers of antibody- producing cells were determined by ELISPOT and the levels of immunoglo bulin in the sera by isotype-specific enzyme-linked immunosorbent assa y. We observed an increased [H-3]thymidine ([H-3]TdR) incorporation by spleen cells after rTc24 stimulation in vivo and in vitro. This proli ferative activity induced by rTc24 was independent of the mouse strain used in the experiments (including C3H/HeJ mice) and ruled out the po ssibility that rTc24 preparations were contaminated by lipopolysacchar ide. The injection of rTc24 protein induced preferentially the activat ion of B cells, as determined by the increased expression of CD69 mole cules on IgM(+) spleen cells. Considerable increases of IgM-secreting B cells were determined in both athymic and euthymic BALB/c mice. Mice that are deficient in B cells (BALB.Xid) responded to rTc24 but to a lesser extent. These increases in IgM B-cell numbers were accompanied by elevated levels of IgM immunoglobulins in the sera of injected anim als. Our results suggest a role for rTc24 in B-cell activation.