CD4 T cells mediate mucosal and systemic immune responses to experimental hookworm infection

Hookworm infection is associated with anaemia and malnutrition in many resource-limited countries. Ancylostoma hookworms have previously been shown to modulate host cellular immune responses through multiple mechanisms, including reduced mitogen-mediated lymphocyte proliferation, impaired antigen presentation/processing, and relative reductions in CD4(+) T cells in the spleen and mesenteric lymph nodes. Syrian hamsters were depleted of CD4(+) for up to 9 days following intraperitoneal injection (200 microg) of a murine anti-mouse CD4 monoclonal IgG (clone GK1.5). CD4(+) T-cell-depleted hamsters infected with the hookworm Ancylostoma ceylanicum exhibited a threefold higher mean intestinal worm burden and more severe anaemia than animals that received isotype control IgG. In addition, depletion of CD4(+) T cells was associated with impaired cellular and humoral (serum and mucosal) immune responses to hookworm antigens. These data demonstrate an effector role for CD4(+) T cells in hookworm immunity and disease pathogenesis. Ultimately, these studies may yield important insights into the relationship between intestinal nematode infections and diseases that are associated with CD4(+) T-cell depletion, including HIV.