Human CD38 and its ligand CD31 define a unique lamina propria T lymphocyte signaling pathway.
CD38, a nonlineage-restricted surface glycoprotein, is an ecto-enzyme (ADP ribosyl cyclase/cADPR hydrolase/EC 3.2.2.6) that regulates cytoplasmic Ca2+ and cell-cell interactions. The molecule also delivers trans-membrane signals, despite a structural ineptitude to the scope. To reconcile these issues in a unitarian model, we compared the effects of CD38 signaling in circulating and residential T lymphocytes, the latter represented by those colonizing the intestinal lamina propria. Results are as follows: 1) LP T cells express an enzymatically active form of CD38, characterized by a modified ratio between cyclase and hydrolase functions; 2) LP T cells do not mobilize Ca2+ upon CD38 ligation, as seen in PB T cells (this condition is due to a lack in activation of PLC- g, constantly observed in PB T lymphocytes); 3) The early steps of CD38 signaling involve activation of lck, syk, and LAT; 4) Late events include synthesis and release of IL-2, IL-4, IL-5, IL-10, IFN-g and GM-CSF; 5) The uniqueness of the CD38 pathway in LP T cells is not caused by impaired interactions with the CD31 ligand. The differences observed concern the signaling machinery that CD38 exploits for its own use and not the interplay with its ligand.
Laboratory of Immunogenetics, Department of Genetics, First Surgical, University of Torino Medical School, Torino, Italy.
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S
Deaglio
R
R
Mallone
G
G
Baj
D
D
Donati
G
G
Giraudo
F
F
Corno
S
S
Bruzzone
M
M
Geuna
C
C
Ausiello
F
F
Malavasi
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002469:Cell Separation; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D019169:Jurkat Cells; D008562:Membrane Glycoproteins; D008954:Models, Biological; D009092:Mucous Membrane / Q000166:cytology / Q000378:metabolism*; D009097:Multienzyme Complexes; D009244:NAD+ Nucleosidase / Q000235:genetics / Q000378:metabolism*; D051966:Phospholipase C gamma; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D011233:Precipitin Tests; D015398:Signal Transduction / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D016207:Cytokines; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D009097:Multienzyme Complexes; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1; D002118:Calcium