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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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

Cite this

Phythian-Adams, A. T., Cook, P. C., Lundie, R. J., Jackson-Jones, L. H., Smith, K. A., Barr, T. A., ... MacDonald, A. S. (2010). CD11c depletion severely disrupts Th2 induction and development in vivo. Journal of Experimental Medicine, 207(10), 2089-2096. https://doi.org/10.1084/jem.20100734
Phythian-Adams, Alexander T. ; Cook, Peter C. ; Lundie, Rachel J. ; Jackson-Jones, Lucy H. ; Smith, Katherine A. ; Barr, Tom A. ; Hochweller, Kristin ; Anderton, Stephen M. ; Hämmerling, Günter J. ; Maizels, Rick M. ; MacDonald, Andrew S. / CD11c depletion severely disrupts Th2 induction and development in vivo. In: Journal of Experimental Medicine. 2010 ; Vol. 207, No. 10. pp. 2089-2096.
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Phythian-Adams, AT, Cook, PC, Lundie, RJ, Jackson-Jones, LH, Smith, KA, Barr, TA, Hochweller, K, Anderton, SM, Hämmerling, GJ, Maizels, RM & MacDonald, AS 2010, 'CD11c depletion severely disrupts Th2 induction and development in vivo', Journal of Experimental Medicine, vol. 207, no. 10, pp. 2089-2096. https://doi.org/10.1084/jem.20100734

CD11c depletion severely disrupts Th2 induction and development in vivo. / Phythian-Adams, Alexander T.; Cook, Peter C.; Lundie, Rachel J.; Jackson-Jones, Lucy H.; Smith, Katherine A.; Barr, Tom A.; Hochweller, Kristin; Anderton, Stephen M.; Hämmerling, Günter J.; Maizels, Rick M.; MacDonald, Andrew S.

In: Journal of Experimental Medicine, Vol. 207, No. 10, 27.09.2010, p. 2089-2096.

Research output: Contribution to journalArticleResearchpeer-review

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Phythian-Adams AT, Cook PC, Lundie RJ, Jackson-Jones LH, Smith KA, Barr TA et al. CD11c depletion severely disrupts Th2 induction and development in vivo. Journal of Experimental Medicine. 2010 Sep 27;207(10):2089-2096. https://doi.org/10.1084/jem.20100734