4-1BB-dependent inhibition of immunosuppression by activated CD4+CD25+ T cells

Journal of Leukocyte Biology

Beom K. Choi³  Shimon Sakaguchi⁴  Byoung S. Kwon¹  Woo J. Kang³  Jun S. Bae³  Dass S. Vinay²  Eun M. Choi³ 

[1] Immunomodulation Research Center, University of Ulsan, Korea; Louisiana State University Eye Center, Louisiana State University Health Sciences Center School of Medicine, New Orleans Immunomodulation Research Center, University of Ulsan, Korea; Immunomodulation Research Center, University of Ulsan, Korea; Louisiana State University Eye Center, Louisiana State University Health Sciences Center School of Medicine, New Orleans Louisiana State University Eye Center, Louisiana State University Health Sciences Center School of Medicine, New Orleans Immunomodulation Research Center, University of Ulsan, Korea; Louisiana State University Eye Center, Louisiana State University Health Sciences Center School of Medicine, New Orleans;Louisiana State University Eye Center, Louisiana State University Health Sciences Center School of Medicine, New Orleans Louisiana State University Eye Center, Louisiana State University Health Sciences Center School of Medicine, New Orleans Louisiana State University Eye Center, Louisiana State University Health Sciences Center School of Medicine, New OrleansImmunomodulation Research Center, University of Ulsan, Korea; Immunomodulation Research Center, University of Ulsan, Korea; Immunomodulation Research Center, University of Ulsan, Korea;;Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Japan; and Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Japan; and Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Japan; and

关键词: regulatory T lymphocytes;    GVHD;    tolerance;    suppression;   

DOI  :  10.1189/jlb.1003491

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

4-1BB (CD137) is a costimulatory molecule involved in the activation and survival of CD4, CD8, and natural killer cells. Although a great deal has been learned as to how 4-1BB-mediated signaling governs the immunity of conventional T cells, the functional role of 4-1BB in the context of CD4+CD25+ regulatory T cell (Tr) activation is largely unknown. Using 4-1BB-intact and -deficient mice, we investigated the effect of the 4-1BB/4-1BB ligand pathway on the suppressive function of Tr cells. Our data indicate that although 4-1BB is expressed on Tr cells, its contribution to their proliferation is minimal. We also showed that signaling through the 4-1BB receptor inhibited the suppressive function of Tr cells in vitro and in vivo. It is interesting that anti-4-1BB-mediated but not anti-GITR-directed inhibition was more potent when Tr cells were preactivated. Collectively, these data indicate that 4-1BB signaling is critical in Tr cell immunity.

【 授权许可】

Unknown