Agonistic anti‐4‐1BB antibody promotes the expansion of natural regulatory T cells while maintaining Foxp3 expression

P Zhang, F Gao, Q Wang, X Wang, F Zhu… - Scandinavian …, 2007 - Wiley Online Library
P Zhang, F Gao, Q Wang, X Wang, F Zhu, C Ma, W Sun, L Zhang
Scandinavian journal of immunology, 2007Wiley Online Library
The engagement of the 4‐1BB (CD137) co‐stimulatory pathway promotes the activation and
proliferation of conventional CD4+ T and CD8+ T cells, but the role of 4‐1BB co‐stimulation
in CD4+ CD25+ regulatory T cells (Treg) is less clear. In particular, whether 4‐1BB
stimulation affects the expression of Foxp3, a master gene for Treg, is unknown. This study
demonstrates that co‐stimulation of 4‐1BB engaged by an agonistic antibody promotes the
proliferation of Treg in a dependent manner of low‐concentration interleukin‐2 in vitro. The 4 …
Abstract
The engagement of the 4‐1BB (CD137) co‐stimulatory pathway promotes the activation and proliferation of conventional CD4+ T and CD8+ T cells, but the role of 4‐1BB co‐stimulation in CD4+ CD25+ regulatory T cells (Treg) is less clear. In particular, whether 4‐1BB stimulation affects the expression of Foxp3, a master gene for Treg, is unknown. This study demonstrates that co‐stimulation of 4‐1BB engaged by an agonistic antibody promotes the proliferation of Treg in a dependent manner of low‐concentration interleukin‐2 in vitro. The 4‐1BB‐expanded Treg maintain Foxp3 expression and their ability to suppress conventional CD4+ T cells and their feature to produce no interleukin‐2. However, the 4‐1BB‐expanded Treg produce increased levels of interferon‐γ, whose significance is unknown. Thus, 4‐1BB co‐stimulation plays a role in the expansion of functional CD4+ CD25+ Treg cells without adversely affecting their suppressive activity.
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