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We previously observed that mice bearing the autoimmune associated lpr gene exhibit increased susceptibility to challenge with Trypanosoma cruzi, the causative agent of Chagas' disease. We have now tested two other autoimmune prone strains of mice, BXSB and NZB, and found that these animals also show increased sensitivity to acute T. cruzi infection. When challenged with a standard dose (10(2)) of Y strain trypomastigotes, BXSB males (BXSB-YSB), which develop early onset autoimmune disease, suffered high mortality, while late onset autoimmune BXSB females and minimally autoimmune male BXSB mice whose Y chromosome was derived from C57BL/6J mice (BXSB-YB/6) also recover. NZB mice were found to be highly susceptible to challenge while NZW and NZB/W were resistant. A finding common to all groups of susceptible autoimmune mice was increased plasma levels of T. cruzi specific antibody, especially IgM. The data indicate that in two of the three autoimmune prone strains examined, increased T. cruzi susceptibility appears to be linked to restricted genetic elements (i.e. lpr gene and the YSB associated factor) which also influence the rapidity of onset of autoimmunity.

Mice with self-limiting P. yoelii or fatal P. berghei infections exhibited a markedly impaired ability to mount specific splenic cytotoxic T-lymphocyte responses to immunization with infectious ectromelia (EV), vaccinia (VAC), or lymphocytic choriomeningitis viruses (LCMV). Lymph node responsiveness, however, was not impaired. Primary CTL responses were depressed in mice immunized 7 days after P. berghei infection, while in P. yoelii-infected mice, depressed responses were detected only during the period corresponding with maximal parasitemia (days 9-12). Secondary VAC-specific CTL responses in vitro by spleen cells of mice previously immunized during P. yoelii infection were also depressed if UV-inactivated rather than infectious VAC was used for immunization. In addition, spleen cells of mice already immune to VAC failed to yield normal secondary CTL responses in vitro during the period of maximal P. yoelii parasitaemia. Collectively, these findings indicate that, during patent malaria infections, priming for and expression of virus-specific CTL responses may be inhibited.