Influence of sphingolipids on T lymphocyte activation

Abstract

Sphingolipid metabolism in immune cells results in formation of a second lipid messenger, e.g., ceramide, sphingosine, ceramide-1-phosphate, and sphingosine-1-phosphate. They are involved in a common signaling which controls the main stages of the lymphocyte development, differentiation, activation, and proliferation in response to a mitogenic and antigenic stimuli, and to initiate programmed cell death. Both, the sphingomyelin cycle products and inhibitor of ceramide synthase--fumonisin B1--have been shown to affect the CD3, CD4, CD8, CD45, and other T lymphocyte surface antigen expression, to disrupt lymphocyte subpopulation balance, to inhibit DNA synthesis in normal lymphocytes, and to suppress an immune response to T-dependent antigens in vivo. The common targets of the TCR/CD3-derived and sphingolipid-mediated signaling pathways may provide the sphingolipid effect on immune cells.