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Infection and Immunity, July 2005, p. 4034-4042, Vol. 73, No. 7
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.7.4034-4042.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Regulatory T Cells Modulate Th2 Responses Induced by Brugia pahangi Third-Stage Larvae

Victoria Gillan and Eileen Devaney*

Parasitology Group, Institute of Comparative Medicine, University of Glasgow, Garscube Estate, Bearsden Road, Glasgow G61 1QH, United Kingdom

Received 26 November 2004/ Returned for modification 9 January 2005/ Accepted 25 February 2005

Infection of BALB/c mice with Brugia pahangi third-stage larvae (L3) results in the production of interleukin-4 (IL-4), IL-5, and IL-10 with a resultant down-regulation in Th1 responses. Previously, this was thought to reflect a skewing of immune responses towards a Th2 phenotype by the infective stage of the parasite. In this study, we show that exposure to the L3 of Brugia also induces the expansion of a population of CD4 cells that express CD25 and cytotoxic-T-lymphocyte-associated antigen 4 in an IL-4-independent fashion. By quantitative reverse transcription-PCR, we show that the CD25+ population is highly enriched in mRNA for the Foxp3 transcription factor and that these cells express significantly more IL-10 mRNA than the CD25– population, suggesting a likely regulatory phenotype. The functional capacity of these cells was demonstrated using a neutralizing CD25 monoclonal antibody (MAb). Mice treated with this MAb demonstrated elevated levels of antigen (Ag)-specific proliferation in vitro, and levels of Ag-specific Th2 cytokines were significantly increased. These results suggest a complex network of regulation in L3-infected mice with Th2 cells limiting the Th1 response, while T-regulatory cells modulate Th2 responses.

* Corresponding author. Mailing address: Parasitology Group, Institute of Comparative Medicine, University of Glasgow, Garscube Estate, Bearsden Road, Glasgow G61 1QH, United Kingdom. Phone: 44-141-330-6925. Fax: 44-141-330-5603. E-mail: e.devaney{at}vet.gla.ac.uk.

Editor: J. F. Urban, Jr.

Infection and Immunity, July 2005, p. 4034-4042, Vol. 73, No. 7
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.7.4034-4042.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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