Published online before print December 23, 2003
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,1
* Immunomodulation Research Center, University of Ulsan, Korea;
Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Japan; and
Louisiana State University Eye Center, Louisiana State University Health Sciences Center School of Medicine, New Orleans
1 Correspondence: Immunomodulation Research Center, University of Ulsan, 29 Mukeo-Dong, Nam-Ku, Ulsan, Korea, 680-749. E-mail: bskwon{at}mail.ulsan.ac.kr
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.
Key Words: regulatory T lymphocytes • GVHD • tolerance • suppression
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