CD44 co-stimulates apoptosis in thymic lymphomas and T cell hybridomas.
Thymic lymphomas and hybridomas vary in their sensitivity to dexamethasone (DEX). Identical variance has been demonstrated in our laboratory for apoptosis of such cells by primary thymic epithelial cells or a cell line (TEC). We have also shown that apoptosis induced by TEC was partially mediated by TEC-derived glucocorticoids (GC). We studied the responses of various thymic lymphomas and hybridomas to TEC and DEX. Of these cells, PD1.6 and 2B4 were sensitive whereas B10 were relatively resistant to either inducer. In the present study we found that TEC and DEX synergize in inducing B10 cell apoptosis. B10 cells could also undergo apoptosis by TEC, conditional upon the presence of a TEC-sensitive cell (PD1.6 or 2B4). Contact between TEC and B10 was essential for apoptosis to occur. Thus, TEC may provide two signals, one mediated by GC and the other requiring cell to cell contact. We then analyzed the involvement of co-stimulatory or adhesion molecules in the TEC-induced apoptosis of thymic lymphoma cells. Soluble anti-CD44 antibodies but not anti-CD18, CD2 or CD28, inhibited TEC-induced apoptosis of PD1.6. Dimerization of CD44 by immobilized antibodies augmented DEX-induced apoptosis of all the lymphomas tested. CD44 cross-linkage up-regulated expression of the pro-apoptotic protein Bax, and down-regulated the anti-apoptotic protein, Bclx(L), in the presence of DEX. Taken together, the data suggest that CD44 enhances the apoptotic response of T lymphoma cells to DEX, and that CD44 modulates TEC-induced apoptosis of thymic lymphomas.
Guy
R
R
The Lautenberg Center for General and Tumor Immunology, The Hebrew University, Hadassah Medical School, P.O. Box 12272, 91120 Jerusalem, Israel.
Yefenof
E
E
Naor
D
D
Dorogin
A
A
Zilberman
Y
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D002999:Clone Cells; D018920:Coculture Techniques; D003907:Dexamethasone / Q000494:pharmacology; D019281:Dimerization; D015536:Down-Regulation; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D005938:Glucocorticoids / Q000494:pharmacology; D018960:Hyaluronan Receptors / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D006825:Hybridomas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D005938:Glucocorticoids; D018960:Hyaluronan Receptors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D003907:Dexamethasone