Monoclonal antibody to CD4+ T cells abrogates genetic resistance to Haemonchus contortus in sheep.
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.
Gill
H S
HS
Department of Animal Science, University of New England, Armidale, New South Wales, Australia.
Watson
D L
DL
Brandon
M R
MR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology; D006188:Haemonchiasis / Q000276:immunology* / Q000469:parasitology / Q000662:veterinary*; D006400:Hematocrit; D007113:Immunity, Innate / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology; D012756:Sheep; D012757:Sheep Diseases / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens