Ceramide-independent CD28 and TCR signaling but reduced IL-2 secretion in T cells of acid sphingomyelinase-deficient mice.
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.
Stoffel
B
B
Institute of Medical Microbiology and Hygiene, University of Cologne, Germany.
Bauer
P
P
Nix
M
M
Deres
K
K
Stoffel
W
W
D000818:Animals; D018106:CD28 Antigens / Q000502:physiology*; D002478:Cells, Cultured; D002518:Ceramides / Q000502:physiology*; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D008247:Lysosomes / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000172:deficiency*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*
D018106:CD28 Antigens; D002518:Ceramides; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D013108:Sphingomyelin Phosphodiesterase