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 (AAMPhi) 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.
Department of Pathology, University of California-San Francisco, San Francisco, CA 94143, USA.
P'ng
P
Loke
Xingxing
X
Zang
Lisa
L
Hsuan
Rebecca
R
Waitz
Richard M
RM
Locksley
Judith E
JE
Allen
James P
JP
Allison
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007074:Immunoglobulin G / Q000378:metabolism; D060889:Inducible T-Cell Co-Stimulator Protein; D036341:Intercellular Signaling Peptides and Proteins; D015847:Interleukin-4 / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009349:Nematode Infections / Q000276:immunology*; D020932:Nerve Growth Factor / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; C556694:Icos protein, mouse; D007074:Immunoglobulin G; D060889:Inducible T-Cell Co-Stimulator Protein; D036341:Intercellular Signaling Peptides and Proteins; D037102:Lectins; D011506:Proteins; C413576:Retnla protein, mouse; D015847:Interleukin-4; D020932:Nerve Growth Factor; C429541:Chil3 protein, mouse; D001619:beta-N-Acetylhexosaminidases