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| Article Authors: | Berent J Prakken; Rodrigo Samodal; Tho D Le; Francesca Giannoni; Gisella Puga Yung; John Scavulli; Diane Amox; Sarah Roord; Isme de Kleer; Dustan Bonnin; Paola Lanza; Charles Berry; Margherita Massa; Rosario Billetta; Salvatore Albani |
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| Article Title: | Epitope-specific immunotherapy induces immune deviation of proinflammatory T cells in rheumatoid arthritis. |
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| Reference ID: | 1014545 |
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| Abstract: | Modulation of epitope-specific immune responses would represent a major addition to available therapeutic options for many autoimmune diseases. The objective of this work was to induce immune deviation by mucosal peptide-specific immunotherapy in rheumatoid arthritis (RA) patients, and to dissect the related immunological mechanisms by using a technology for the detection of low-affinity class II-restricted peptide-specific T cells. A group of patients with early RA was treated for 6 months orally with dnaJP1, a peptide that induces proinflammatory T cell responses in naive RA patients. Immunological analysis at initial, intermediate and end treatment points showed an intriguing change from proinflammatory to regulatory T cell function. In fact, dnaJP1-induced T cell production of IL-4 and IL-10 increased significantly when initial and end treatment points were compared, whereas dnaJP1-induced T cell proliferation and production of IL-2, IFN-gamma, and tumor necrosis factor-alpha decreased significantly. The total number of dnaJP1-specific cells did not change over time, whereas expression of foxP3 by CD4+CD25(bright) cells increased, suggesting that the treatment affected regulatory T cell function. Thus, rather than clonal deletion, the observed change in immune reactivity to dnaJP1 was the outcome of treatment-induced emergence of T cells with a different functional phenotype. This study contributes to our knowledge of mechanisms and tools needed for antigen-specific immune modulation in humans, thus laying the foundation for exploitation of this approach for therapeutic purposes. |
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| Affiliations: | Departments of Medicine and Pediatrics, and IACOPO Institute for Translational Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0663, USA. |
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| Date: | 2004 |
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| Reference Type: | Literature |
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| PubMed ID: | 15024101 |
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| Journal: | Proc Natl Acad Sci U S A |
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| Journal Volume: | 101 |
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| Article Pages: | 4228-33 |
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| Journal ISSN: | 0027-8424 |
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| Article Chemical List: | Adjuvants, Immunologic;DNA-Binding Proteins;Epitopes;FOXP3 protein, human;Forkhead Transcription Factors;Heat-Shock Proteins;Receptors, Interleukin-2 |
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| Article MeSH List: | Adjuvants, Immunologic(pharmacology); Arthritis, Rheumatoid(immunology; therapy); CD4-Positive T-Lymphocytes(drug effects; immunology); DNA-Binding Proteins(drug effects); Epitopes(immunology); Female; Forkhead Transcription Factors; Heat-Shock Proteins(pharmacology); Humans; Immunity, Mucosal(drug effects; immunology); Immunotherapy; Male; Middle Aged; Receptors, Interleukin-2(drug effects); T-Lymphocytes(drug effects; immunology) |
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| Curation Last Updated: | 2010-10-26 02:09:24 |
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