Ligation of the lymphocyte homing receptor CD44 triggers T-helper and cytolytic functions of human T cells.
We show that antibodies to the CD44 molecule trigger proliferation of human CD3+/CD4+ T-cell clones. Such effect is IL2-dependent, as shown by IL2 production induced by anti-CD44 mAb and by inhibition of cell proliferation in the presence of anti-IL2 antibodies or cyclosporin A (CsA). Moreover, anti-CD44 mAb triggered human cytolytic CD4+ and CD8+ TCR alpha/beta+ clones, and V delta 1 or V delta 2 TCR Y/delta+ clones to lyse Fc-gamma-R+ P815 cells and to release granule trypsin-like esterase enzymes. Anti-CD44 mAb-triggered proliferation and cytotoxicity were blocked by the PTK-inhibitor, genestein. In addition, ligation of the CD44 molecule induced tyrosine phosphorylation of proteins identical, by molecular weight, to those phosphorylated following anti-CD3 mAb-stimulation. Notably, anti-CD44 mAb does not induce tyrosine phosphorylation of a 21 kD protein (the phosphorylated zeta chain of the TcR molecular complex) typically observed upon anti-CD3 mAb stimulation.
Galandrini
R
R
Inst of Hematol, Univ of Perugia, Genova, Italy.
Albi
N
N
Vecchiarelli
A
A
Tognellini
R
R
Zarcone
D
D
Grossi
C E
CE
Velardi
A
A
D000911:Antibodies, Monoclonal; D001709:Biotechnology; D002455:Cell Division; D002999:Clone Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D011505:Protein-Tyrosine Kinases / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000037:antagonists & inhibitors / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016201:Receptors, Lymphocyte Homing; D011505:Protein-Tyrosine Kinases