Autocrine nitric oxide modulates CD95-induced apoptosis in gammadelta T lymphocytes.
Gammadelta T lymphocytes play an important early role in the defense against pathogens. Their function is terminated by acquisition of susceptibility to CD95-triggered apoptosis. Here we show that the regulation of this process depends on the activity of the endothelial NO synthase expressed by gammadelta T lymphocytes, which is modulated in an activation-dependent way. The effects of nitric oxide thus generated, mediated via cGMP generation, are exerted at at least two sites along the CD95 signaling cascade: one at, or upstream, and the other downstream of ceramide generation. At either site, nitric oxide/cGMP action is sufficient for protection from apoptosis. The effect of NO is selective for apoptosis induced by CD95 cross-linking, since it does not affect apoptotic program triggered by other stimuli. The evidence here reported demonstrates a new physiological role for nitric oxide, acting as a survival factor for T lymphocytes.
Sciorati
C
C
Receptor Biochemistry Unit, DIBIT, University of Reggio Calabria, 88021 Catanzaro and Consiglio Nazionale delle Ricerche Cellular and Molecular Pharmacology Centre, Via Olgettina 58, 20132 Milano, Italy.
Rovere
P
P
Ferrarini
M
M
Heltai
S
S
Manfredi
A A
AA
Clementi
E
E
D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism; D002999:Clone Cells; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D018448:Models, Immunological; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism*
D002518:Ceramides; D007527:Isoenzymes; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019014:fas Receptor; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D002118:Calcium