Th2 Cell-Intrinsic Hypo-Responsiveness Determines Susceptibility to Helminth Infection

摘要: The suppression of protective Type 2 immunity is a principal factor driving the chronicity helminth infections, and has been attributed to range Th2 cell-extrinsic immune-regulators. However, intrinsic fate parasite-specific cells within chronic immune down-regulatory environment, resultant impact such changes may have on host resistance unknown. We used IL-4gfp reporter mice demonstrate that during infection with filarial nematode Litomosoides sigmodontis, CD4+ are conditioned towards an intrinsically hypo-responsive phenotype, characterised by loss functional ability proliferate produce cytokines IL-4, IL-5 IL-2. cell hypo-responsiveness was key element determining susceptibility L. sigmodontis infection, could be reversed in vivo blockade PD-1 resulting long-term recovery quality enhanced resistance. Contrasting T dysfunction 1 settings, control mediated through PD-L2, not PD-L1. Thus, leading functionally phenotype play role therapeutic manipulation cell-intrinsic provides potential avenue for promoting helminths.