Effects of 4-1BB Signaling on the Biological Function of Murine Dendritic Cells

Overview

Journal Oncol Lett

Specialty Oncology

Date 2012 Jun 29

PMID 22740935

Citations 10

Authors

Youlin Kuang

Xiaodong Weng

Xiuheng Liu

Hengchen Zhu

Zhiyuan Chen

Hui Chen

Affiliations

Soon will be listed here.

Abstract

4-1BB signaling has profound effects on the T cell-induced cell immune response, but its biological function in dendritic cells (DCs) has remained largely uncharacterized. In this study, we investigated the function of 4-1BB in murine DCs with an agonistic mAb to 4-1BB. Interleukin (IL)-6 and IL-12 production was assessed by an enzyme-linked immunosorbent assay (ELISA). Co-stimulatory molecules (CD80 and CD86) in DCs were analyzed by flow cytometry. The results showed that 4-1BB was strongly expressed in DCs during the maturation process. Triggering 4-1BB increased the secretion of IL-6 and IL-12 and the upregulation of co-stimulatory molecules (CD80 and CD86) from DCs, indicating that agonistic mAb to 4-1BB directly improves the activation of DCs. Moreover, triggering 4-1BB induced a higher survival rate of DCs compared to that of hamster IgG isotype control, due to the upregulated expression of Bcl-2 and Bcl-xL. To further assess the role of 4-1BB on DCs stimulating T-cell proliferation, allogeneic mixed lymphocyte reactions were analyzed. The agonistic anti-4-1BB mAb induced a higher T-cell proliferation. These results suggest that 4-1BB affects the duration, DC-T interaction and immunogenicity of DCs.

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