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.