CD11c depletion severely disrupts Th2 induction and development in vivo

Alexander T. Phythian-Adams, Peter C. Cook, Rachel J. Lundie, Lucy H. Jackson-Jones, Katherine A. Smith, Tom A. Barr, Kristin Hochweller, Stephen M. Anderton, Günter J. Hämmerling, Rick M. Maizels, Andrew S. MacDonald

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206 Citations (Scopus)

Abstract

Although dendritic cells (DCs) are adept initiators of CD4+ T cell responses, their fundamental importance in this regard in Th2 settings remains to be demonstrated. We have used CD11c - diphtheria toxin (DTx) receptor mice to deplete CD11c+ cells during the priming stage of the CD4+ Th2 response against the parasitic helminth Schistosoma mansoni. DTx treatment significantly depleted CD11c+ DCs from all tissues tested, with 70-80% efficacy. Even this incomplete depletion resulted in dramatically impaired CD4+ T cell production of Th2 cytokines, altering the balance of the immune response and causing a shift toward IFN-γ production. In contrast, basophil depletion using Mar-1 antibody had no measurable effect on Th2 induction in this system. These data underline the vital role that CD11c+ antigen-presenting cells can play in orchestrating Th2 development against helminth infection in vivo, a response that is ordinarily balanced so as to prevent the potentially damaging production of inflammatory cytokines.

Original languageEnglish
Pages (from-to)2089-2096
Number of pages8
JournalJournal of Experimental Medicine
Volume207
Issue number10
DOIs
Publication statusPublished - 27 Sep 2010
Externally publishedYes

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