Open AccessThe BTLA and PD‐1 signaling pathways independently regulate the proliferation and cytotoxicity of human peripheral blood γδ T cells
Author(s) -
Hwang Hyun J.,
Lee Jae J.,
Kang Sung H.,
Suh Jin K.,
Choi Eun S.,
Jang Seongsoo,
Hwang SangHyun,
Koh KyungNam,
Im Ho J.,
Kim Nayoung
Publication year - 2021
Publication title -
immunity, inflammation and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 18
ISSN - 2050-4527
DOI - 10.1002/iid3.390
Subject(s) - btla , jurkat cells , t cell , cytotoxic t cell , microbiology and biotechnology , signal transduction , phosphorylation , t lymphocyte , biology , protein tyrosine phosphatase , cytotoxicity , flow cytometry , chemistry , immunology , immune system , biochemistry , in vitro
Background B‐ and T‐lymphocyte attenuator (BTLA) and programmed cell death‐1 (PD‐1) inhibit γδ T cell homeostasis and activation. This study aimed to determine whether BTLA and PD‐1 signaling pathways were convergent or independent in human peripheral blood γδ T cells. Herein we demonstrate that the signalings of BTLA and PD‐1 regulated proliferation and cytotoxicity of human γδ T cells, respectively. Methods Human peripheral blood γδ T cells were cultured with inactivated Jurkat cells in the presence of interleukin‐2 and zoledronate (Zol) for 14 days. Flow cytometry was performed to evaluate the phenotypes and functions of γδ T cells. Results The proliferation of the γδ T cells was increased when PBMCs were cocultured with inactivated herpes virus entry mediator (HVEM) low Jurkat cells. The cytotoxicity of the expanded γδ T cells was not affected by coculture with inactivated HVEM low Jurkat cells and was further increased in the presence of anti‐PD‐L1 mAb. These results suggest that the inactivation of the BTLA signaling pathway during expansion could help produce more γδ T cells without compromising γδ T cell function. The inhibition of BTLA or PD‐1 signaling repressed phosphorylation of the src homology region 2‐containing protein tyrosine phosphatase 2 and increased the phosphorylation of protein kinase B in γδ T cells. However, there were no synergistic or additive effects by a combination of BTLA and PD‐1 blockade. Conclusion These results suggest that BTLA signaling is crucial in regulating γδ T cell proliferation and function and that the BTLA and PD‐1 signaling pathways act independently on the proliferation and cytotoxicity of human peripheral γδ T cells.