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

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 (T_reg) cells, dominantly inhibit induction and progression of autoimmunity as shown in several autoimmune models. In humans, the presence of T_reg cells has been shown, but their role in autoimmune disease is not known. Likewise, no (auto)antigens recognized by T_reg cells have yet been identified at the molecular level. The aim of these studies is to gain a better understanding of the identity of (auto)antigens recognized by T_reg cells.

Results

When analyzing the natural T-cell response against a candidate autoantigen in rheumatoid arthritis, human cartilage glycoprotein-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 production of 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 cytotoxic T lymphocyte 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 recognised by T_reg cells in humans.