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.
Takai
Shinji
S
Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Tokuda
Haruhiko
H
Matsushima-Nishiwaki
Rie
R
Saio
Masanao
M
Takami
Tsuyoshi
T
Kozawa
Osamu
O
D028341:Activins / Q000276:immunology; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D007371:Interferon-gamma / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D012834:Silver / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000276:immunology
D055415:Bone Morphogenetic Protein 4; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D028341:Activins; D012834:Silver; D007371:Interferon-gamma; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I