The BTLA and PD‐1 signaling pathways independently regulate the proliferation and cytotoxicity of human peripheral blood γδ T cells
| العنوان: | The BTLA and PD‐1 signaling pathways independently regulate the proliferation and cytotoxicity of human peripheral blood γδ T cells |
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| المؤلفون: | Ho J Im, Kyung-Nam Koh, Eun Sun Choi, Jae J Lee, Sung H Kang, Seongsoo Jang, Hyun J Hwang, Sang-Hyun Hwang, Jin Kyung Suh, Nayoung Kim |
| المصدر: | Immunity, Inflammation and Disease, Vol 9, Iss 1, Pp 274-287 (2021) Immunity, Inflammation and Disease |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, lcsh:Immunologic diseases. Allergy, T-Lymphocytes, T cell, proliferation, Programmed Cell Death 1 Receptor, Immunology, BTLA, Protein tyrosine phosphatase, Jurkat cells, Peripheral blood mononuclear cell, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, medicine, human peripheral blood γδ T cells, Humans, Immunology and Allergy, Receptors, Immunologic, Protein kinase B, Cell Proliferation, Original Research, medicine.diagnostic_test, Chemistry, AKT, PD‐1, Cell biology, 030104 developmental biology, medicine.anatomical_structure, SHP2, cytotoxicity, Signal transduction, lcsh:RC581-607, Signal Transduction, 030215 immunology |
| الوصف: | 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 HVEMlow 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. Blocking B‐ and T‐lymphocyte attenuator (BTLA) signaling increases γδ T cell proliferation ex vivo. BTLA signaling regulates γδ T cell proliferation and programmed cell death‐1 regulates effector function without affecting the other. |
| اللغة: | English |
| تدمد: | 2050-4527 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2d37fba8ce50d2d8a4c911cb4f74144f https://doaj.org/article/f0f15260c3cf4ca5bfc9af231f8f8791 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....2d37fba8ce50d2d8a4c911cb4f74144f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20504527 |
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