TGF-beta superfamily enhances the antigen-induced IFN-gamma production by effector/memory CD8+ T cells.

Ag-specific effector/memory CD8+ T cells play an important role, not only in viral eradication, but also in T cell-mediated tumor rejection. Increasing evidence suggests that TGF-beta plays a critical role in the tumor escape from immune surveillance. Although it is known that TGF-beta directly suppresses the activation of naïve T cells, the direct effects of TGF-beta on effector/memory CD8+ T cells have not yet been fully investigated. The present study evaluated the effect of TGF-beta on effector/memory CD8+ T cells using Ag-specific, mouse-derived, effector/memory CD8+ T cell clones, designated as 6C2. Notably, pretreatment of TGF-beta1 caused an approximate 100% enhancement of IFN-gamma production in response to peptide stimulation. TGFbeta-RI kinase inhibitor reduced the enhancement of peptide-induced IFN-gamma secretion by TGF-beta1. In addition, either Activin-A or BMP-4 pretreatment caused an approximate 100% enhancement of IFN-gamma production in the peptide effect. These results suggest a contradictory effect of the TGF-beta superfamily on effector/memory CD8+ T cells.