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Epitope-specific immunotherapy induces immune deviation of proinflammatory T cells in rheumatoid arthritis
- Source :
- Proceedings of the National Academy of Sciences. 101:4228-4233
- Publication Year :
- 2004
- Publisher :
- Proceedings of the National Academy of Sciences, 2004.
-
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-γ, and tumor necrosis factor-α decreased significantly. The total number of dnaJP1-specific cells did not change over time, whereas expression of foxP3 by CD4+CD25brightcells 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.
- Subjects :
- CD4-Positive T-Lymphocytes
Male
Regulatory T cell
T-Lymphocytes
T cell
Biology
Arthritis, Rheumatoid
Epitopes
Interleukin 21
Immune system
Adjuvants, Immunologic
medicine
Humans
IL-2 receptor
Immunity, Mucosal
Heat-Shock Proteins
Multidisciplinary
FOXP3
Forkhead Transcription Factors
Receptors, Interleukin-2
Middle Aged
Biological Sciences
Acquired immune system
DNA-Binding Proteins
medicine.anatomical_structure
CTLA-4
Immunology
Female
Immunotherapy
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 101
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....944572408bb9cff5d69841a59fe446f6