IL-27 is a heterodimeric cytokine of IL-12 family consisted of p28 and EBI3 subunits, and have regulatory function for T cell immune responses. We previously reported that a subpopulation of malaria antigen-specific Foxp3- CD4+ T cells produce IL-27 and inhibit IL-2 production as well as proliferation of other CD4+ T cells during infection with malaria parasites.
Malaria antigen-specific Th1 cells are induced during the infection with Plasmodium berghei ANKA, and play critical roles for the protection against the infection. However, these Th1 cells disappeared quickly after the cure from the infection by anti-malaria drug treatment. We hypothesized that T cell-derived IL-27 may contribute to the loss of memory responses after the cure. To test this hypothesis, we compared the memory responses between C57BL/6 and Il27p28-/- mice after infection and cure with P. berghei ANKA. Memory responses of CD4+ T-cells were quickly lost in C57BL/6 mice after the cure, while they were maintained in IL-27p28-/- mice. Apoptosis of malaria-specific CD4+ T cells was accelerated in C57BL/6 mice when compared with Il27p28-/- mice during the treatment. In addition, parasite-specific antibody responses were higher in Il27p28-/- mice. After the re-challenge, IL-27p28-/- mice showed little parasitema, and their CD4+ T cells exhibited enhanced IFN-γ response. These results suggest that IL-27 inhibits the generation of memory CD4+ T cells by accelerating apoptosis of parasite-specific CD4+ T cells during contraction phase of the immune response against P. berghei ANKA.