Epitope-specific immunotherapy induces immune deviation of proinflammatory T cells in rheumatoid arthritis

BJ Prakken, R Samodal, TD Le… - Proceedings of the …, 2004 - National Acad Sciences
BJ Prakken, R Samodal, TD Le, F Giannoni, GP Yung, J Scavulli, D Amox, S Roord…
Proceedings of the National Academy of Sciences, 2004National Acad Sciences
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 …
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+CD25bright 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.
National Acad Sciences