Dataset Information

The BTLA and PD-1 signaling pathways independently regulate the proliferation and cytotoxicity of human peripheral blood ?? T cells.

ABSTRACT:

Background

B- and T-lymphocyte attenuator (BTLA) and programmed cell death-1 (PD-1) inhibit ?? 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 ?? T cells. Herein we demonstrate that the signalings of BTLA and PD-1 regulated proliferation and cytotoxicity of human ?? T cells, respectively.

Methods

Human peripheral blood ?? 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 ?? T cells.

Results

The proliferation of the ?? T cells was increased when PBMCs were cocultured with inactivated herpes virus entry mediator (HVEM)^low Jurkat cells. The cytotoxicity of the expanded ?? 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 ?? T cells without compromising ?? 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 ?? 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 ?? T cell proliferation and function and that the BTLA and PD-1 signaling pathways act independently on the proliferation and cytotoxicity of human peripheral ?? T cells.

SUBMITTER: Hwang HJ

PROVIDER: S-EPMC7860523 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

The BTLA and PD-1 signaling pathways independently regulate the proliferation and cytotoxicity of human peripheral blood γδ T cells.

Hwang Hyun J HJ Lee Jae J JJ Kang Sung H SH Suh Jin K JK Choi Eun S ES Jang Seongsoo S Hwang Sang-Hyun SH Koh Kyung-Nam KN Im Ho J HJ Kim Nayoung N

Immunity, inflammation and disease 20201217 1

<h4>Background</h4>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.<h4>Methods</h4>Human peripheral blood γδ T cells were cultured with inactivated Jurkat ...[more]

PMID: 33332777

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