4-1BB promotes the survival of CD8+ T lymphocytes by increasing expression of Bcl-xL and Bfl-1.
4-1BB, a T cell costimulatory receptor, prolongs CD8(+) T cell survival. In these studies, 4-1BB stimulation was shown to increase expression of the antiapoptotic genes bcl-x(L) and bfl-1 via 4-1BB-mediated NF-kappaB activation. This signaling pathway was specifically inhibited by PDTC and was different from the pathways that enhanced CD8(+) T cell proliferation. The results suggest a role for the antiapoptotic activities of Bcl-x(L) and Bfl-1 proteins in 4-1BB-mediated CD8(+) T cell survival in vivo.
Lee
Hyeon-Woo
HW
Immunomodulation Research Center, University of Ulsan, Korea.
Park
Su-Jung
SJ
Choi
Beom K
BK
Kim
Hyun Hwa
HH
Nam
Kyung-Ok
KO
Kwon
Byoung S
BS
D053330:4-1BB Ligand; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD; D017209:Apoptosis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002867:Chromones / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation; D048728:MAP Kinase Kinase Kinase 1; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015778:Minor Histocompatibility Antigens; D009025:Morpholines / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D011759:Pyrrolidines / Q000494:pharmacology; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D013859:Thiocarbamates / Q000494:pharmacology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D015854:Up-Regulation / Q000276:immunology; D051020:bcl-X Protein
D053330:4-1BB Ligand; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D002867:Chromones; D005419:Flavonoids; D008024:Ligands; D048728:MAP Kinase Kinase Kinase 1; D015778:Minor Histocompatibility Antigens; D009025:Morpholines; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D019253:Proto-Oncogene Proteins c-bcl-2; D011759:Pyrrolidines; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; D013859:Thiocarbamates; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha; D051020:bcl-X Protein; C096816:BCL2-related protein A1; C494812:Bcl2l1 protein, mouse; C505715:Tnfrsf9 protein, mouse; C505975:Tnfsf9 protein, mouse; C020972:pyrrolidine dithiocarbamic acid; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C482578:Map3k1 protein, mouse; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one