Human cartilage glycoprotein 39-directed T cell responses in health and arthritic diseases

  • JHM van Bilsen1,

    Affiliated with

    • LR Lard1,

      Affiliated with

      • EIH van der Voort1,

        Affiliated with

        • D Elferink2,

          Affiliated with

          • A Bakker1,

            Affiliated with

            • H van Dongen1,

              Affiliated with

              • AMM Miltenburg3,

                Affiliated with

                • T Huizinga1,

                  Affiliated with

                  • R de Vries2 and

                    Affiliated with

                    • REM Toes1

                      Affiliated with

                      Arthritis Res Ther20046(Suppl 1):7

                      DOI: 10.1186/ar1049

                      Received: 16 January 2004

                      Published: 24 February 2004

                      Objective

                      Although (self)antigen-directed T cells are thought to be key mediators of many autoimmune diseases, a functionally distinct population of CD4+ T cells – T regulatory cells (Treg cells) – dominantly inhibit induction and progression of autoimmunity, as demonstrated in several autoimmune models. In humans the presence of Treg cells has been shown, but their role in autoimmune disease is not known. Likewise, no (auto)antigens recognized by Treg cells have yet been identified at the molecular level. The aim of these studies was to gain a better understanding of the identity of (auto)antigens recognized by Treg cells.

                      Results

                      When analyzing the natural T cell response against a candidate autoantigen in rheumatoid arthritis (RA), namely human cartilage gp-39 (HC gp-39), we found that healthy donors, although displaying a typical Th1 reaction against a mixture of recall antigens, reacted against HC gp-39 by producing IL-10. The IL-10 production was mediated by CD4+ T cells. When HC gp-39-directed immunity of RA patients was analyzed, a marked contrast was observed as Th1-like reactivity was observed in a substantial number of patients as determined by the production of IFN-γ. More importantly, we found that HC gp-39-directed immunity in healthy donors inhibits the T cell response against a mixture of recall antigens. Likewise, HC gp-39-specific immunity as well as HC gp-39-directed, IL-10-producing CD4+ T cell lines were able to suppress MHC class I-restricted CTL reactivity.

                      Conclusion

                      Together, these data point to a disease-associated bias in the type of T cell response against HC gp-39, and identify HC gp-39 as a naturally occurring autoantigen that is recognized by Treg cells in humans.

                      Authors’ Affiliations

                      (1)
                      Department of Rheumatology, Leiden University Medical Center
                      (2)
                      Department of Immunohematology and Blood Transfusion, Leiden University Medical Center
                      (3)
                      Organon BV

                      Copyright

                      © BioMed Central Ltd 2004

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