Epitope-Specific Immunotherapy Induces Immune Deviation of Proinflammatory T Cells in Rheumatoid Arthritis

• Published in: Proceedings of the National Academy of Sciences - PNAS 2004-03, Vol.101 (12), p.4228-4233
• Main Authors: Prakken, Berent J., Samodal, Rodrigo, Le, Tho D., Giannoni, Francesca, Yung, Gisella Puga, Scavulli, John, Amox, Diane, Roord, Sarah, de Kleer, Isme, Bonnin, Dustan, Lanza, Paola, Berry, Charles, Massa, Margherita, Billetta, Rosario, Albani, Salvatore, Carson, Dennis A.
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - pharmacology; Antigens; Arthritis; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - therapy; Autoimmune diseases; Biological Sciences; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; Cytokines; DNA-Binding Proteins - drug effects; Drug therapy; Epitopes - immunology; Female; Forkhead Transcription Factors; Gene expression; Heat-Shock Proteins - pharmacology; Humans; Immunity, Mucosal - drug effects; Immunity, Mucosal - immunology; Immunology; Immunotherapy; Joint diseases; Male; Medical research; Middle Aged; Molecules; Receptors, Interleukin-2 - drug effects; Rheumatoid arthritis; T lymphocytes; T-Lymphocytes - drug effects; T-Lymphocytes - immunology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0400061101

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.