Regulatory T cells modulate Th2 responses induced by Brugia pahangi third-stage larvae.
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.
Parasitology Group, Institute of Comparative Medicine, University of Glasgow, Garscube Estate, Bearsden Road, Glasgow G61 1QH, United Kingdom.
Victoria
V
Gillan
Eileen
E
Devaney
D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis; D017179:Brugia pahangi / Q000276:immunology*; D060908:CTLA-4 Antigen; D004268:DNA-Binding Proteins / Q000032:analysis; D005368:Filariasis / Q000276:immunology*; D051858:Forkhead Transcription Factors; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000502:physiology; D007814:Larva; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000502:physiology*; D018418:Th2 Cells / Q000276:immunology*; D014157:Transcription Factors / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000235:genetics
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; C556708:Ctla4 protein, rat; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma