Inducible costimulator is required for type 2 antibody isotype switching but not T helper cell type 2 responses in chronic nematode infection

Inducible costimulator (ICOS) has been suggested to perform an important role in T helper cell type 2 (Th2) responses, germinal center formation, and isotype switching. The role of ICOS in chronic Th2 responses was studied in a nematode model with the filarial parasite, Brugia malayi. Contrary to expectations, we did not observe a significant defect in IL-4-producing Th2 cells in ICOS-/mice or in eosinophil recruitment. We also found that ICOS was not required for the differentiation of alternatively activated macrophages (AAM[PHI]) that express Ym1 and Fizz1. Although the production of IgE was slightly reduced in ICOS-/- mice, this was not as significant as in CD28-/- mice. In contrast to live infection, the primary response of ICOS-/- mice immunized with soluble B. malayi antigen and complete Freund's adjuvant resulted in significantly fewer IL-4-producing cells in the lymph nodes. As previously reported, we observed a defect in antibody isotype switching toward the IgG1 isotype in ICOS-/- mice during live infection. Interestingly, there was a significant enhancement of parasite-specific IgG3 isotype antibodies. CD28-/- and MHC class II-/mice also had enhanced parasite-specific IgG3 isotype antibodies. Our results suggest that ICOS is not required to maintain a chronic cellular Th2 response. The primary role of ICOS in a chronic helminth infection could be to drive antibodies toward type 2 isotypes. T-independent antibody response to the parasite could be enhanced in the absence of costimulation and T cell help. allergy | costimulation | helminth | IgE | inflammation