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International Immunology Advance Access originally published online on March 14, 2008
International Immunology 2008 20(5):659-669; doi:10.1093/intimm/dxn025
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© The Author 2008. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved.
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press and The Japanese Society for Immunology are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Gr1+IL-4-producing innate cells are induced in response to Th2 stimuli and suppress Th1-dependent antibody responses

Amy S. McKee1, Megan MacLeod1, Janice White1, Frances Crawford1, John W. Kappler1,2,3 and Philippa Marrack1,3,4

1 Integrated Department of Immunology, National Jewish Medical and Research Center, Howard Hughes Medical Institute, 1400 Jackson Street, CO 80206, USA
2 Department of Pharmacology
3 Department of Medicine, University of Colorado Health Science Center, Denver, CO 80262, USA
4 Program in Biomolecular Structure, Department of Biochemistry and Molecular Genetics

Correspondence to: P. Marrack; E-mail: marrackp{at}njc.org

Alum is used as a vaccine adjuvant and induces Th2 responses and Th2-driven antibody isotype production against co-injected antigens. Alum also promotes the appearance in the spleen of Gr1+IL-4+ innate cells that, via IL-4 production, induce MHC II-mediated signaling in B cells. To investigate whether these Gr1+ cells accumulate in the spleen in response to other Th2-inducing stimuli and to understand some of their functions, the effects of injection of alum and eggs from the helminth, Schistosoma mansoni, were compared. Like alum, schistosome eggs induced the appearance of Gr1+IL-4+ cells in spleen and promoted MHC II-mediated signaling in B cells. Unlike alum, however, schistosome eggs did not promote CD4 T cell responses against co-injected antigens, suggesting that the effects of alum or schistosome eggs on splenic B cells cannot by themselves explain the T cell adjuvant properties of alum. Accordingly, depletion of IL-4 or Gr1+ cells in alum-injected mice had no effect on the ability of alum to improve expansion of primary CD4 T cells. However, Gr1+ cells and IL-4 played some role in the effects of alum, since depletion of either resulted in antibody responses to antigen that included not only the normal Th2-driven isotypes, like IgG1, but also a Th1-driven isotype, IgG2c. These data suggest that alum affects the immune response in at least two ways: one, independent of Gr1+ cells and IL-4, that promotes CD4 T cell proliferation and another, via Gr1+IL-4+ cells, that participates in the polarization of the response.

Keywords: antibodies, helminth, T cells, Th2, vaccine adjuvant


Transmitting editor: S. Hedrick

Received 4 September 2007, accepted 13 February 2008.


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