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| Content Provider | PubMed Central |
|---|---|
| Author | Singh, Kameshwar P. Gerard, Herve C. Hudson, Alan P. Reddy, Thipparthi R. Boros, Dov L. |
| Copyright Year | 2005 |
| Abstract | Schistosomiasis mansoni, a tropical helminthic disease, is caused by disseminated worm eggs that induce CD4+ T-cell mediated granulomatous inflammation and fibrosis. T suppressor cell activity has been proposed as one of the mechanisms active in the down-modulation of the murine disease during the chronic stage (16–20 weeks of the infection). In recent years a new category of the CD4+ CD25+ T regulatory (Treg) lymphocyte has been identified that maintains immune tolerance to self, and also functions in the regulation of parasite-induced immunopathology. The Foxp3 gene which encodes the transcription factor Scurfin was found to be expressed by and required for the generation of CD4+ CD25+ T reg. At 8 weeks of the infection Foxp3 gene expression of splenocytes was similar to that of naïve mice, but increased fourfold by 16 weeks. In contrast, granulomatous livers at 8 and 16 weeks showed 10- and 30-fold increases, respectively, in gene expression compared with normal liver. The percentage of granuloma CD4+ CD25+ T cells rose from 12% at 8 weeks to 88% at 16 weeks of the infection. Foxp3 expression was 3·5-fold higher in the CD4+ CD25+ versus the CD4+ CD25− T cells in the 8 week infection granulomas. As a novel observation neuropilin-1 membrane expression, a recently identified marker for Treg, was correlated with Foxp3 expression in the granuloma CD4+ CD25+ but not the CD25− cells. Co-incubation with polyclonal stimulation of CD4+ CD25+ splenic cells with CD4+ CD25− cells suppressed proliferation of the latter. Retroviral transfer of the Foxp3 gene at the onset of granuloma formation enhanced fourfold Foxp3 expression in the granuloma CD4+ CD25+ T cells and strongly suppressed full granuloma development. Gene transfer also significantly enhanced transforming growth factor-β, interferon-γ and interleukin-4 but not interleukin-10 expression. It is concluded, that CD4+ CD25+, Foxp3+ Treg cells also regulate schistosome egg-induced immunopathology. |
| Related Links | http://dx.doi.org/10.1111/j.1365-2567.2004.02083.x |
| Ending Page | 417 |
| Page Count | 8 |
| Starting Page | 410 |
| File Format | |
| ISSN | 00192805 |
| e-ISSN | 13652567 |
| Journal | Immunology |
| Issue Number | 3 |
| Volume Number | 114 |
| Language | English |
| Publisher | Blackwell Science Inc |
| Publisher Date | 2005-03-01 |
| Access Restriction | Open |
| Rights Holder | Blackwell Science Inc |
| Subject Keyword | Immunology Immunology and Allergy Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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