CTLA-4 LIGANDS ARE REQUIRED TO INDUCE AN IN-VIVO INTERLEUKIN-4 RESPONSE TO A GASTROINTESTINAL NEMATODE PARASITE

The costimulatory signal provided to T cells through CTLA-4-ligand int eractions is required for T cell activation resulting in increased int erleukin 2 (IL-2) production in vitro, but its role in the production of IL-4 and other cytokines is unclear and few in vivo studies have be en performed to confirm results of in vitro experiments. We have exami ned the in vivo effects of blocking CTLA-4 ligands on the T helper cel l 2 (Th2)-associated mucosal immune response that follows oral infecti on of mice with the nematode parasite, Heligmosomoides polygyrus. CTLA -4Ig administration inhibited H. polygyrus-induced increases in mesent eric lymph node (MLN) B cell major histocompatibility complex class II expression and size and T cell-derived IL-4 gene expression. In addit ion, CTLA-4 immunoglobulin (Ig) partially blocked increased IL-3, IL-5 , and IL-9 cytokine gene expression in Peyer's patch (PP) and MLN 8 d after primary inoculation of mice with the parasite. Increases in the number of IL-4- but not IL-5-secreting cells were also inhibited by CT LA-4Ig. H. polygyrus-induced elevations in serum IgE levels but not bl ood eosinophils, were markedly inhibited by CTLA-4Ig. These results su ggest that stimulation of CD28 and/or CTLA-4 is required for T cell pr iming leading to IL-4 cytokine production, B cell activation, and IgE secretion during a Th2-like, mucosal immune response to a nematode par asite.