H. polygyrus: B7-independence of the secondary type 2 response

The gastrointestinal nematode parasite, Heligmosomoides polygyrus, has been used extensively in experimental studies of host immunity. The pronounced type 2 primary immune response to H. polygyrus is associated with elevated CD4+, TCR-alpha/beta + T cell IL-4 production and elevated serum IgE levels that are blocked by inhibiting CD28/ CTLA4-B7 interactions following in vivo administration of the chimeric fusion protein, CTLA4Ig. In the present study, we have examined the in vivo effects of blocking CTLA4Ig ligands on the secondary type 2 mucosal host protective immune response to this parasite. Our results show that although CD4+, TCR-alpha/beta + cells remain the primary source of elevated IL-4 during the secondary response, the protective immune response and the effector cell activity associated with it is B7-independent as CTLA4Ig administration at the time of challenge does not block (1) elevations in T cell IL-4 gene expression or protein secretion; (2) elevations in serum IgE levels, mucosal mastocytosis, or eosinophilia; or (3) host protection, as measured by adult worm burden and fecundity. These findings suggest that memory T helper cells do not require CD28-B7 interactions for their activation to effector cells that can mediate a host protective type 2 immune response.