Ceramide-independent CD28 and TCR signaling but reduced IL-2 secretion in T cells of acid sphingomyelinase-deficient mice

Abstract

Ceramide generated by lysosomal acid sphingomyelinase (aSMase) has been proposed to contribute to CD28 co‐stimulatory signaling pathways. We used an aSMase‐deficient mouse line ( asmase^{− / −}) to elucidate the role of the aSMase in splenocytes stimulated with either a combination of anti‐CD3 and anti‐CD28 antibodies, the lectin concanavalin A (Con A) or the superantigen staphylococcal enterotoxin B. All stimuli were shown to induce IL‐2 expression, Con A additionally triggered the expression of high‐affinity IL‐2 receptor. However, in asmase^{− / −} mice secretion of IL‐2 was significantly reduced, whereas the intracellular IL‐2 levels were elevated. Proliferation of anti‐CD3/anti‐CD28 or Con A‐stimulated aSMase‐deficient splenocytes was reduced up to 50 % after 72 h in comparison to wild‐type cells. We conclude that ceramide generated by aSMase is not involved in CD28 signal transduction, but rather a perturbation of the secretory system is responsible for the impaired proliferation of aSMase‐deficient splenocytes.