Co-stimulation of antigen-specific CD4 T cells by 4-1BB ligand

Role of costimulatory pathways in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis

“…161 There appears to be a preferential role for CD137 in the costimulation of CD8 + T cells, 162,163 although CD4 + T-cell costimulation has also been reported. 164,165 CD137 can provide CD28-independent costimulation; however, it is most effective in the presence of a strong TCR signal. 166 Signaling through the CD137 pathway can induce the preferential expansion of CD8 + cytotoxic T lymphocytes that in turn can enhance tumor rejection.…”

Interfacing T-cell effector and regulatory function through CD137 (4-1BB) co-stimulation

“…Two days after in vitro peptide stimulation, T cells express CD137 [5,6]; however, CD137 expression in vivo occurs earlier after stimulation with superantigen or peptide [7,8]. Although expression can be prolonged [9], in general, CD137 expression on activated T cells is transient.…”

“…For example, proliferation [6,20], survival [7,20], cytokine production [21,22] and cytotoxic killing activity are enhanced profoundly by CD137 co-stimulation [21,23]. Some of these effects are also true for CD4 C T cells [5,6,8]. Importantly, in these experiments, CD137 was studied through T-cell stimulation with a variety of methods, including peptide, whole protein, superantigen and mitogenic stimulation, all in the face of inhibiting or activating CD137.…”

Exploiting 4-1BB Costimulation for Enhancing Antiviral Vaccination

“…There have been several reports of 4-1BB costimulation improving CD4 ϩ T cell proliferation, cytokine production, and survival in vitro (6,12,28) and in vivo (3,16,38). However, there have also been some reports that 4-1BB signaling has no effect on CD4 ϩ T cells (5,75).…”