Activation and IL-10 production of specific CD4 T cells are regulated by IL-27 during chronic infection with Plasmodium chabaudi.

IL-27, a regulatory cytokine, plays critical roles in the prevention of immunopathology during Plasmodium infection. We examined these roles in the immune responses against Plasmodium chabaudi infection using the Il-27ra mice. While IL-27 was expressed at high levels during the early phase of the infection, enhanced CD4 T cell function and reduction in parasitemia were observed mainly during the chronic phase in the mutant mice. In mice infected with P. chabaudi and cured with drug, CD4 T cells in the Il-27ra mice exhibited enhanced CD4 T-cell responses, indicating the inhibitory role of IL-27 on the protective immune responses. To determine the role of IL-27 in detail, we performed CD4 T-cell transfer experiments. The Il-27ra and Il27p28 mice were first infected with P. chabaudi and then cured using drug treatment. Plasmodium-antigen primed CD4 T cells were prepared from these mice and transferred into the recipient mice, followed by infection with the heterologous parasite P. berghei ANKA. Il-27ra CD4 T cells in the infected recipient mice did not produce IL-10, indicating that IL-10 production by primed CD4 T cells is IL-27 dependent. Il27p28 CD4 T cells that were primed in the absence of IL-27 exhibited enhanced recall responses during the challenge infection with P. berghei ANKA, implying that IL-27 receptor signaling during the primary infection affects recall responses in the long-term via the regulation of the memory CD4 T cell generation. These features highlighted direct and time-transcending roles of IL-27 in the regulation of immune responses against chronic infection with Plasmodium parasites.