DIFFERENTIAL SUSCEPTIBILITIES OF MICE GENOMICALLY DELETED OF CD4 AND CD8 TO INFECTIONS WITH TRYPANOSOMA-CRUZI OR TRYPANOSOMA-BRUCEI

The role of CD4(+) and CD8(+) T cells in the surveillance of Trypanosoma cruzi or Trypanosoma brucei bricei was studied in mice which lacked CD4 or CD8 molecules and which were generated by embryonic stem cell technology. Whereas wild-type mice infected with T. cruzi (Tulahuen strain) displayed low levers of parasitemia and no mortality, striking increases in parasite growth and mortality occurred in both CD8(-) and CD4(-) mice. On the contrary, CD8(-) and, to a lesser degree, CD4(-) mice showed enhanced resistance to T. b. brucei. T-cell-dependent immunoglobulin G-specific responses were produced in CD8(-) but not CD4(-) mice. Normal T-cell proliferative responses were measured in both CD4(-) and CD8(-) mice. Interleukin-4 production after concanavalin A or anti-CD3 monoclonal antibody stimulation was strikingly enhanced in CD8(-) but not CD4(-) spleen cells, whereas gamma interferon production was normal in both CD4(-) and CD8(-) spleen cells. Spleen and lymph node cells from CD8(-) (but not CD4(-)) mice at 20 days postinfection with T. cruzi had higher levels of interleukin-4 mRNA than the wild-type controls, as shown in a competitive polymerase chain reaction assay. On the other hand, CD4(-) (but not CD8(-)) mice at 20 days postinfection with T. cruzi had lower levels of gamma interferon mRNA than the wild-type mice.