They noted that CD28 engagement induced a higher level of ceramide production, whereas CD3 stimulation triggered minimal ceramide generation, suggesting an important role of ASM in CD28 signaling.11 Others have noted that combinations of anti-CD3 (10 μg/ml) and anti-CD28 (1 μg/ml) antibodies induce IL-2 production in ASM deficiency splenocytes, and concluded that both CD3 and CD28 signal transductions were independent of ASM bioactivity and ceramide generation.14 However, another group reported that ASM was involved in modulating CD3/CD28 signaling in human CD4+ T cells.10 Here, CD4 is linked to aggressive systemic mastocytosis.