Antigen-specific IL-4- and IL-10-secreting CD4 super(+) lymphocytes increase in vivo susceptibility to Trypanosoma cruzi infection

• Published in: Cellular immunology 1996-05, Vol.170 (1), p.41-53
• Main Authors: Barbosa de Oliveira, LC, Curotto de Lafaille, MA, De Araujo Lima, GMC, De Almeida Abrahamsohn, I
• Format: Article
• Language: English
• Subjects: Trypanosoma cruzi
• ISSN: 0008-8749

Control of macrophage parasiticidal function by treatment with recombinant cytokines or their neutralizing antibodies modifies the severity of experimental Trypanosoma cruzi infections. However, so far, no direct in vivo evidence has demonstrated changes in disease outcome after altering the initial ratios of parasite-specific IFN- gamma and IL-10/IL-4-secretor cells in secondary lymphoid organs. To this end, a population of predominantly CD4 super(+) parasite-Ag-reactive, IL-4- and IL-10-secreting T lymphocytes derived from T. cruzi immunized mice was adoptively transferred to naive recipients. Compared with cell responses from normal mice, spleen cells of uninfected recipients proliferated significantly to T. cruzi Ag and produced much greater amounts of IL-4 and IL-10; lower IFN- gamma levels and increased IL-4/IL-10 levels were induced by Con A stimulation. Recipient mice challenged with T. cruzi presented 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 super(+), 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- gamma 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- gamma secretion reversed the host's resistance to T. cruzi. Moreover, transfer of anti-T. cruzi Th2-type cells most likely favored the in vivo expansion of parasite-specific host toward a Th2 phenotype.