In conclusion, we have described an essential role for IL-27 signaling in preventing early mortality of mice infected with African trypanosomes through dampening IFN-γ secretion by CD4+ T cells, thus identifying, in addition to previously described IL-10 signaling, a novel pathway for maintenance of immunological balance during infection with extracellular protozoan parasites African trypanosomes. This evidence concerns the gene CD4 and infection.