The 4-1BB costimulation augments the proliferation of CD4+CD25+ regulatory T cells.
The thymus-derived CD4(+)CD25(+) T cells belong to a subset of regulatory T cells potentially capable of suppressing the proliferation of pathogenic effector T cells. Intriguingly, these suppressor cells are themselves anergic, proliferating poorly to mitogenic stimulation in culture. In this study, we find that the 4-1BB costimulator receptor, best known for promoting the proliferation and survival of CD8(+) T cells, also induces the proliferation of the CD4(+)CD25(+) regulatory T cells both in culture and in vivo. The proliferating CD4(+)CD25(+) T cells produce no detectable IL-2, suggesting that 4-1BB costimulation of these cells does not involve IL-2 production. The 4-1BB-expanded CD4(+)CD25(+) T cells are functional, as they remain suppressive to other T cells in coculture. These results support the notion that the peripheral expansion of the CD4(+)CD25(+) T cells is controlled in part by costimulation.
Department of Biomedical Sciences, College of Medicine, University of Illinois, Rockford, IL 61107, USA. guoxingz@uic.edu
Guoxing
G
Zheng
Bin
B
Wang
Aoshuang
A
Chen
D000818:Animals; D015703:Antigens, CD; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D018189:Immunomagnetic Separation; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D017475:Receptors, Nerve Growth Factor / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
D015703:Antigens, CD; D015704:CD4 Antigens; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505715:Tnfrsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9