Antigen-Specific IL-4- and IL-10-Secreting CD4+Lymphocytes Increasein VivoSusceptibility toTrypanosoma cruziInfection

Control of macrophage parasiticidal function by treatment with recombinant cytokines or their neutralizing antibodies modifies the severity of experimentalTrypanosoma cruziinfections. However, so far, no directin vivoevidence has demonstrated changes in disease outcome after altering the initial ratios of parasite-specific IFN-γ and IL-10/IL-4-secretor cells in secondary lymphoid organs. To this end, a population of predominantly CD4+parasite-Ag-reactive, IL-4- and IL-10-secreting T lymphocytes derived fromT. cruzi-immunized mice was adoptively transferred to naive recipients. Compared with cell responses from normal mice, spleen cells of uninfected recipients proliferated significantly toT. cruziAg and produced much greater amounts of IL-4 and IL-10; lower IFN-γ levels and increased IL-4/IL-10 levels were induced by Con A stimulation. Recipient mice challenged withT. cruzipresented overwhelming tissue and blood parasitemia and early death, contrasting with typically resistant controls. Uninfected recipients did not exhibit tissue damage following cell transfer. No disease exacerbation occurred in recipients of OVA-reactive CD4+, IL-4/IL-10-secreting T lymphocytes stimulated with OVA at the start of infection. On Day 6 postinfection, not only spleen cells but also LN cells from infected recipients showed decreased production of IFN-γ and augmented secretion of IL-4/IL-10 compared to cells from untransferred infected mice. The results indicate that an imbalance of Th cell populations leading to the predominance of secreted IL-4 and IL-10 at the start of infection and the concomitant down-regulation of IFN-γ secretion reversed the hostʹs resistance toT. cruzi.Moreover, transfer of anti-T. cruziTh2-type cells most likely favored thein vivoexpansion of parasite-specific host cells toward a Th2 phenotype.