CTLA-4 and CD4+ CD25+ regulatory T cells inhibit protective immunity to filarial parasites in vivo.

摘要: The T cell coinhibitory receptor CTLA-4 has been implicated in the down-regulation of function that is a quintessential feature chronic human filarial infections. In laboratory model filariasis, Litomosoides sigmodontis infection susceptible BALB/c mice, we have previously shown susceptibility linked both to CD4+ CD25+ regulatory (Treg) response, and development hyporesponsive cells at site, pleural cavity. We now provide evidence L. drives proliferation activation Foxp3+ Treg vivo, demonstrated by increased uptake BrdU expression CTLA-4, Foxp3, GITR, CD25 compared with naive controls. greatest increases were, however, seen Foxp3- effector population which contained 78% all CTLA-4+ Depletion from did not increase their Ag-specific proliferative response vitro, suggesting phenotype directly mediated cells. Once had established, killing adult parasites could be enhanced neutralization but only if performed combination depletion This work suggests during coinhibition form complementary components immune regulation inhibit protective immunity vivo.