Interestingly, CD28 also seems to play a central role in the regulation of IFNγ production, since several studies reported that CD4+ CD28- T cells secrete large amounts of IFNγ and have been associated with Th1-driven autoimmune diseases such as multiple sclerosis of rheumatoid arthritis [6, 48–50]. This evidence concerns the gene CD4 and rheumatoid arthritis.