Monoclonal antibody to CD4+ T cells abrogates genetic resistance to Haemonchus contortus in sheep.

Abstract

The roles of CD4+ and CD8+ T cells in genetically determined resistance of sheep to Haemonchus contortus (a natural host-parasite relationship) was investigated by selectively depleting genetically resistant merino lambs of their CD4+ or CD8+ T cells by treatment with mouse monoclonal antibody (mAb) specific for the appropriate determinant before and during challenge infection. Administration of anti-CD4 mAb to genetically resistant lambs completely abrogated their expression of genetic resistance as indicated by significantly higher faecal egg output and worm burdens found in the CD4+ T-cell-depleted lambs compared with those of controls. Host responses associated with resistance to H. contortus including mucosal mast cell hyperplasia and tissue eosinophilia were also significantly suppressed in CD4-depleted lambs. The development of anamnestic anti-parasite antibody responses were also significantly inhibited by anti-CD4 mAb. Furthermore, anti-CD4 mAb abolished differences in host responses between genetically resistant and random-bred (susceptible) lambs. In contrast, depletion of CD8+ T cells had no effect on genetic resistance; faecal egg output, worm counts, mast cells and eosinophil responses in CD8-depleted lambs were not significantly different from those in controls. Together, these results suggest that CD4+ T cells play a pivotal role in mediating genetic resistance to H. contortus, and in the generation of mucosal mast cell hyperplasia, tissue eosinophilia and anti-Haemonchus antibody. CD8+ T cells appear to play no protective role. The possible mechanisms by which CD4+ T cells might mediate anti-parasite resistance are discussed.