Antibodies to CD44 trigger effector functions of human T cell clones.
mAb against the lymphocyte homing receptor CD44/Hermes up-regulate the proliferation of human T PBL induced by anti-CD3 or anti-CD2 mAb. Moreover, certain anti-CD44 mAb can activate human resting T cells and mouse cytotoxic T cells in the absence of anti-CD3 or anti-CD2 mAb. Here, we show that anti-CD44 mAb trigger proliferation of human CD3+/CD4+ T cell clones in a fashion similar to that observed with mAb to CD3. Such an effect is IL-2-dependent, as shown by IL-2 production induced by anti-CD44 mAb and by complete inhibition of cell proliferation in the presence of anti-IL-2 antibodies or cyclosporin A. Moreover, anti-CD44 mAb trigger human cytolytic T cell clones to lyse Fc gamma-R+ P815 cells in the absence of additional stimuli. The magnitude of the cytolytic response induced by anti-CD44 mAb is comparable to that observed in the presence of anti-CD3 mAb for both CD4+ and CD8+ TCR-alpha/beta+ clones, and for V delta 1 or V delta 2 TCR-gamma/delta+ clones. By contrast, in CD3-/CD16+ NK cell clones, no cytolytic responses to anti-CD44 mAb could be observed. Granule trypsin-like esterase enzyme (granzyme) release by cytolytic T cell clones is induced by plastic-immobilized anti-CD44 mAb. Anti-CD44 mAb-triggered proliferation ([3H]thymidine incorporation) and cytotoxicity are blocked by the protein tyrosine kinase inhibitor, genestein. In addition, ligation of the CD44 molecule induces tyrosine phosphorylation of proteins identical, by molecular mass, to those phosphorylated after anti-CD3 mAb stimulation. Notably, anti-CD44 mAb does not induce tyrosine phosphorylation of a 21-kDa protein (the phosphorylated zeta-chain of the TCR molecular complex) typically observed upon anti-CD3 mAb stimulation. In conclusion, this study shows that the ligated CD44 molecule provides the necessary stimuli for a variety of T cell-mediated functions triggered via protein tyrosine kinase-dependent signal transduction pathways at least in part similar to those that follow stimulation of the CD3/TCR complex.
Galandrini
R
R
Sezione Di Ematologia e Immunologia Clinica, Università di Perugia, Italy.
Albi
N
N
Tripodi
G
G
Zarcone
D
D
Terenzi
A
A
Moretta
A
A
Grossi
C E
CE
Velardi
A
A
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D019833:Genistein; D006801:Humans; D007158:Immunologic Techniques; D066298:In Vitro Techniques; D007529:Isoflavones / Q000494:pharmacology; D008213:Lymphocyte Activation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D007529:Isoflavones; D016201:Receptors, Lymphocyte Homing; D019833:Genistein; D011505:Protein-Tyrosine Kinases