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

P'ng Loke, Xingxing Zang, Lisa Hsuan, Rebecca Waitz, Richard M. Locksley, Judith E. Allen, James P. Allison

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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 (AAMΦ) 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.

Original languageEnglish (US)
Pages (from-to)9872-9877
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number28
DOIs
StatePublished - Jul 12 2005
Externally publishedYes

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Inducible T-Cell Co-Stimulator Protein
Immunoglobulin Class Switching
Nematode Infections
Th2 Cells
Antibodies
Parasites
Brugia malayi
Immunoglobulin G
Interleukin-4
Infection
Germinal Center
Freund's Adjuvant
Helminths
Eosinophils
Immunoglobulin E
Antibody Formation
Lymph Nodes
Macrophages

Keywords

  • Allergy
  • Costimulation
  • Helminth
  • IgE
  • Inflammation

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Inducible costimulator is required for type 2 antibody isotype switching but not T helper cell type 2 responses in chronic nematode infection. / Loke, P'ng; Zang, Xingxing; Hsuan, Lisa; Waitz, Rebecca; Locksley, Richard M.; Allen, Judith E.; Allison, James P.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 28, 12.07.2005, p. 9872-9877.

Research output: Contribution to journalArticle

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