B7RP-1-ICOS interactions are required for optimal infection-induced expansion of CD4+ Th1 and Th2 responses

Emma H. Wilson, Colby Zaph, Markus Mohrs, Andy Welcher, Jerry Siu, David Artis, Christopher A. Hunter

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30 Citations (Scopus)


Although initial reports linked the costimulatory molecule ICOS preferentially with the development of Th2 cells, there is evidence that it is not required for protective type 2 immunity to helminths and that it contributes to Th1 and Th2 responses to other parasites. To address the role of ICOS in the development of infection-induced polarized Th cells, ICOS-/- mice were infected with Trichuris muris or Toxoplasma gondii. Wild-type mice challenged with T. muris developed Th2 responses and expelled these helminths by day 18 postinfection, whereas ICOS-/- mice failed to clear worms and produced reduced levels of type 2 cytokines. However, by day 35 postinfection, ICOS-/- mice were able to mount an effective Th2 response and worms were expelled. This delay in protective immunity was associated with a defect in infection-induced increases in the number of activated and proliferating CD4+ T cells. Similarly, following challenge with T. gondii ICOS was required for optimal proliferation by CD4+ T cells. However, the reduced number of activated CD4+ T cells and associated defect in the production of IFN-γ did not result in increased susceptibility to T. gondii, but rather resulted in decreased CNS pathology during the chronic phase of this infection. Taken together, these data are consistent with a model in which ICOS is not involved in dictating polarity of the Th response but rather regulates the expansion of these subsets.

Original languageEnglish
Pages (from-to)2365-2372
Number of pages8
JournalJournal of Immunology
Issue number4
Publication statusPublished - 15 Aug 2006
Externally publishedYes

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