HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0900577v1 183/6/3906    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Hepworth, M. R. Articles by Grencis, R. K. PubMed PubMed Citation Articles by Hepworth, M. R. Articles by Grencis, R. K. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene Substance via MeSH

Disruption of Th2 Immunity Results in a Gender-Specific Expansion of IL-13 Producing Accessory NK Cells during Helminth Infection¹

Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom

Host gender has previously been identified as a determining factor in the resolution of Trichuris muris infection in mice lacking IL-4 (IL-4KO BALB/c). Worm expulsion in these mice is delayed, but occurs in females. In this study we were able to demonstrate delayed expulsion occurs at day 26 post infection and is associated with the production of the key Th2-associated cytokine IL-13 by both CD4⁺ T cells and an auxiliary DX5⁺ NK cell source, as well as a concurrent reduction in proinflammatory cytokines. NK cell number was comparably increased in both sexes, but NK cells from male mice were found to express higher levels of the chemokine receptor CXCR3. Depletion of CD4⁺ T cells completely prevented parasite expulsion, whereas loss of NK cells resulted in a mild, but significant delay. Furthermore, IL-18 is a cytokine with the capacity to enhance both Th1 and Th2 responses found to be dispensable for worm expulsion in female mice but was a key factor for the suppression of the Th2 response in male IL-4KO mice. In contrast neutralization of IFN- resulted in a complete restoration of typical wild-type BALB/c expulsion kinetics. This study sheds further light on the role of accessory NK cells in supplementing the IL-13-driven immune response when normal Th2 immunity is disrupted, and further identifies host gender as a key factor in determining the generation of "NK cell help".

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by funding from the Medical Research Council U.K. and the Wellcome Trust.

² Address correspondence and reprint requests to Dr. Richard K. Grencis, Faculty of Life Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester M13 9PT, U.K. E-mail address: richard.k.grencis{at}manchester.ac.uk

³ Abbreviations used in this paper: KO, knockout; p.i., postinfection; MLN, mesenteric lymph node; IEL, intraepithelial lymphocyte; E/S, excretory/secretory; WT, wild type.