NK T cells in rheumatoid arthritis

Excerpt

In rheumatoid arthritis (RA), T helper (Th)1 cells, which secrete interferon (IFN)-?, predominate over Th2 cells, which secrete interleukin (IL)-4, IL-5, IL-10 and IL-13. To date, neither the nature of the Th1 predominance nor the relevance to pathogenesis or disease course has been fully understood. Natural killer (NK) T cells have been suggested as a potential source of IL-4 for Th2 differentiation. NK T cells express unique NK cell markers in addition to T cell receptor (TCR)a?. In mice, NK T cells comprise 0.4% of a?-thymocytes but 5% of splenic T cells and 40% of bone marrow T cells. A large fraction of peripheral NK T cells is characterized by expression of the invariant Va14Ja281 TCRa in mice and Va24JaQ in humans (90% homology at the amino acid level in the CDR3 region) and both have restricted TCR V? expression, suggesting the recognition of similar antigens. NK T cells recognize the MHC class I-like CD1d protein. The independent capacity of NK cells to secrete IL-4, in addition to IFN-?, has implicated them in the differentiation of naive T cells into Th2 cells. Interestingly, a more general role for NK T cells in autoimmune disease has been suggested since selective reduction of Va14⁺ NK T cells has been associated with disease development in several autoimmunity-prone mice such as C57BL/6 lpr/lpr, C3H gld/gld or non-obese diabetic mice. Furthermore, in humans, a selective reduction of Va24JaQ⁺ NK T cells, which usually comprise 20-100% of CD4^-CD8^- T cells in healthy people, has been reported in patients with systemic sclerosis and diabetes mellitus type I. To assess the number of NK T cells in patients with RA compared to healthy controls, and any relation between number of NK T cells and activity or severity of the disease. …