In contrast, we find that adaptive, IL-10-producing CD4+ Tr1 cells (CD25−, Foxp3−, CD127−, IFN-γ−, IL-4− and IL-17−), are generated during both PyL and PyNL infections and are associated with down-regulation of pro-inflammatory responses, moderation of both morbidity and mortality and failure to clear parasites. Here, CD4 is linked to Pyle disease.