CD44 (Pgp-1) inhibits CD3 and dexamethasone-induced apoptosis.
Anti-CD3 monoclonal antibodies (MoAbs) and glucocorticoid hormones (GCH) induce apoptosis in immature thymocytes and peripheral T lymphocytes. This process is inhibited by a number of growth factors, including interleukin-2 (IL-2), IL-3, and IL-4, indicating that signals generated by membrane receptors can modulate the survival of lymphoid cells. To investigate whether signals activated by adhesion receptors have a similar activity, we analyzed the effect of CD44 (Pgp-1) adhesion molecule receptor stimulation on T-cell apoptosis induced by three stimuli (anti-CD3 MoAbs, dexamethasone [DEX] treatment, and exposure to ultraviolet irradiation [UV]) on a 3DO T-cell line. The results show that CD44 engagement, either by hyaluronic acid (HA) or anti-CD44 MoAbs, inhibits DNA fragmentation and apoptosis induced by DEX and anti-CD3 MoAbs, whereas that induced by UV, a p53-dependent phenomenon, was not inhibited. Furthermore, the antiapoptotic effect exerted through CD44 activation does not seem related to overexpression of bcl-2 or to have appreciable effects on cell proliferation. Our results indicate that adhesion molecules modulate T-cell survival by counteracting apoptosis induced by DEX or anti-CD3 MoAbs.
Ayroldi
E
E
Department of Clinical Medicine, Pathology and Pharmacology, Perugia University Medical School, Italy.
Cannarile
L
L
Migliorati
G
G
Bartoli
A
A
Nicoletti
I
I
Riccardi
C
C
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D017252:CD3 Complex / Q000276:immunology / Q000494:pharmacology*; D002352:Carrier Proteins / Q000494:pharmacology*; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D018960:Hyaluronan Receptors; D006825:Hybridomas; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D011956:Receptors, Cell Surface / Q000502:physiology; D016201:Receptors, Lymphocyte Homing / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing; D003907:Dexamethasone; D004247:DNA