Serum Amyloid A (SAA) is an acute-phase protein, released predominantly from the liver during large scale inflammation. High SAA levels, up to 1000 times normal, are also associated with autoimmune conditions like Rheumatoid Arthritis (RA). SAA is found in very high levels in the arthritic joints of patients, along with a high concentration of certain subsets of T lymphocytes, notably helper T cell type 1 (Th1). The marker for Th1 cells is production of the cytokine interferon gamma (IFNγ). The purpose of this study is to determine if SAA stimulation of murine T cells causes Th1 differentiation. CD4+ T-cells isolated from the spleens of wild type mice have been stimulated in vitro with SAA protein. IFNγ production was measured and compared to that of the known inducer of Th1 cells, interleukin-12 (IL-12). Indeed, SAA stimulation induced IFNγ production with levels as high as 22,088 pg/mL, which is comparable to the 20,237 pg/mL induced by IL-12. Our data also shows that SAA and IL-12 can co-stimulate T cells and result in even higher levels of IFNγ secretion. Future experiments will confirm Th1 differentiation by detecting cell surface markers with flow cytometry and will also investigate the intracellular actions of SAA stimulation. These results suggest that SAA and Th1 cells are found together in arthritic joints because SAA induces this T-cell subset’s production, and is perhaps a missing link in our understanding of RA.
- Copyright © 2011 by The American Association of Immunologists, Inc.