Elsevier

Seminars in Immunology

Volume 10, Issue 6, December 1998, Pages 481-489
Seminars in Immunology

Regular Article
Role of 4-1BB in immune responses

https://doi.org/10.1006/smim.1998.0157Get rights and content

Abstract

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–κB. 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.

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