Role of 4-1BB in immune responses.
4-1BB is an inducible T cell surface receptor which belongs to the tumor necrosis factor receptor superfamily, a group of cysteine-rich cell-surface molecules. Both human and mouse 4-1BB recently received HLDA nomenclature. Naive T cells lack 4-1BB, which is not only induced upon T cell activation, but also remains on activated T cells. The natural ligand for 4-1BB, 4-1BBL is also induced and is found on activated antigen-presenting cells. Cross-linking of the 4-1BB molecule by agonistic antibody transmits a distinct and potent co-stimulatory signal leading to the activation and differentiation of CD4(+) and CD8(+) cells. 4-1BB transmits signals through the TRAF2-NIK pathway and activates NF-kappaB. Signals relayed through 4-1BB inhibit activation-induced cell death and rescue the immune system during the post-CD28 phase. Antibodies to the 4-1BB molecule can increase GVHD, accelerate the rejection of cardiac allograft and skin transplants, and eradicate established tumors. Interference with the 4-1BB-4-1BBL pathway may be of therapeutic use in the treatment of HIV infection. 4-1BB-deficient mice show dysregulated immune responses and mount elevated Ig responses to T-dependent antigens.
Vinay
D S
DS
Indiana University School of Medicine, and the Walther Oncology Center, 635 Barnhill Drive, Indianapolis, IN, 46202-5120, USA.
Kwon
B S
BS
D053330:4-1BB Ligand; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D017475:Receptors, Nerve Growth Factor / Q000276:immunology* / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology* / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D053330:4-1BB Ligand; D015703:Antigens, CD; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505714:TNFRSF9 protein, human; C505974:TNFSF9 protein, human; C505715:Tnfrsf9 protein, mouse; C505975:Tnfsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha