title: Epitope-specific immunotherapy induces immune deviation of proinflammatory T cells in rheumatoid arthritis.
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.
authors.affiliation: 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.
authors.forename: Berent J
authors.initials: BJ
authors.lastname: Prakken
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Samodal
authors.forename: Tho D
authors.initials: TD
authors.lastname: Le
authors.forename: Francesca
authors.initials: F
authors.lastname: Giannoni
authors.forename: Gisella Puga
authors.initials: GP
authors.lastname: Yung
authors.forename: John
authors.initials: J
authors.lastname: Scavulli
authors.forename: Diane
authors.initials: D
authors.lastname: Amox
authors.forename: Sarah
authors.initials: S
authors.lastname: Roord
authors.forename: Isme
authors.initials: I
authors.lastname: de Kleer
authors.forename: Dustan
authors.initials: D
authors.lastname: Bonnin
authors.forename: Paola
authors.initials: P
authors.lastname: Lanza
authors.forename: Charles
authors.initials: C
authors.lastname: Berry
authors.forename: Margherita
authors.initials: M
authors.lastname: Massa
authors.forename: Rosario
authors.initials: R
authors.lastname: Billetta
authors.forename: Salvatore
authors.initials: S
authors.lastname: Albani
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004268:DNA-Binding Proteins / Q000187:drug effects; D000939:Epitopes / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors; D006360:Heat-Shock Proteins / Q000494:pharmacology; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects / Q000276:immunology; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D004268:DNA-Binding Proteins; D000939:Epitopes; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006360:Heat-Shock Proteins; D015375:Receptors, Interleukin-2