CD28 and autoimmune disease: Autoimmune diseases such as arthritis and inflammatory bowel disease are characterized by CD4+ T-cell overactivation with excessive Th1 and Th17 responses.33, 34, 35 TCR/CD3 signaling cascades in combination with costimulatory CD28 signal induce T-cell activation, cell differentiation and cytokine expression, while dictating the progression of inflammation.28 We speculated that ASM bioactivity could also mediate CD4+ T-cell differentiation and Th cell responses.