4-1BB cross-linking enhances the survival and cell cycle progression of CD4 T lymphocytes.
4-1BB, a T cell co-stimulatory receptor, prolongs the survival and multiplication of CD4 T cells. Cross-linking 4-1BB stimulated expression of the anti-apoptotic genes bcl-XL and bcl-2, as well as of cyclins D2 and E, and inhibited expression of the cyclin-dependent kinase (cdk) inhibitor p27kip1. Ova-activated CD4 T cells of 4-1BB-deficient/DO11.10 TCR transgenic mice survived less well and underwent less expansion than cells of wild type DO11.10 TCR transgenic mice. These findings demonstrate that 4-1BB is a co-stimulatory molecule for CD4 T cell survival and expansion in vivo.
Lee
Hyeon-Woo
HW
The Immunomodulation Research Center and Graduate Program in Immunology and Biomedicine, University of Ulsan, Ulsan 680-749, Republic of Korea. hyeonwoo@mail.ulsan.ac.kr
Nam
Kyung-Ok
KO
Seo
Su K
SK
Kim
Young H
YH
Kang
Hyun
H
Kwon
Byoung S
BS
D000818:Animals; D015703:Antigens, CD; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000187:drug effects; D002470:Cell Survival / Q000502:physiology; D003432:Cross-Linking Reagents / Q000494:pharmacology; D056742:Cyclin D2; D019927:Cyclin E / Q000096:biosynthesis / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000096:biosynthesis / Q000187:drug effects; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D019254:Genes, bcl-2 / Q000187:drug effects / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000502:physiology*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000187:drug effects; D051020:bcl-X Protein
D015703:Antigens, CD; C494812:Bcl2l1 protein, mouse; C486196:Ccnd2 protein, mouse; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D003432:Cross-Linking Reagents; D056742:Cyclin D2; D019927:Cyclin E; D016213:Cyclins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505715:Tnfrsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D025521:Tumor Suppressor Proteins; D051020:bcl-X Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27