Research in pharmaceutical sciences · 2026
PD-1: CD28 chimeric receptors enhance phenotypic and functional features of T cell subsets.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Feghhi-Najafabadi Saba, Riazi-Rad Farhad, Shokrgozar Mohammad Ali, Abdoli Shahriyar, Taheri Fatemeh Hajari, Arashkia Arash, Sharifzadeh Zahra
Аннотация
BACKGROUND AND PURPOSE: The PD-1/PD-L1 immune checkpoint pathway inhibits T cell function, allowing tumors to escape immune responses. This study aimed to reprogram this inhibitory signaling using a PD- 1:CD28 switch receptor (SR) to convert inhibitory signaling into a co-stimulatory signal and to assess its effects on the function of CD4+ and CD8+ T cells.
EXPERIMENTAL APPROACH: PBMCs isolated from both sources were retrovirally transduced with PD-1:CD28 SR. Intracellular expression of cytokines, including IFN-γ, IL-4, IL-10, as well as the surface CD25 in CD4+ and CD8+ T cells, and the rate of cell apoptosis during engineering and exposure to target cells were assessed.
FINDINGS/RESULTS: Both buffy coat (BC) and whole blood showed comparable transduction efficiency (21.4% versus 18.5%, respectively), but BC yielded nearly double the number of viable PBMCs per 50 mL. Upon stimulation and co-culture with target cells, CD4+ SR T cells produced significantly higher levels of IFN-γ, IL-4, and IL-10 compared to CD8+ SR T cells. These cytokines also significantly increased in co-culture supernatants exposed to PD-L1+ cells. No significant differences were found in CD4/CD8 ratios, CD25 expression, or cytokine profiles between PBMC sources. However, BC-derived T cells showed higher apoptosis rates during co-culture.
CONCLUSION AND IMPLICATIONS: BC can be a practical and effective source of PBMCs for T cell engineering. These findings underscore the SR signaling in the activation of CD4+ T cells that may impact the activation of CD8+ T cells, which is essential for effective tumor eradication.
EXPERIMENTAL APPROACH: PBMCs isolated from both sources were retrovirally transduced with PD-1:CD28 SR. Intracellular expression of cytokines, including IFN-γ, IL-4, IL-10, as well as the surface CD25 in CD4+ and CD8+ T cells, and the rate of cell apoptosis during engineering and exposure to target cells were assessed.
FINDINGS/RESULTS: Both buffy coat (BC) and whole blood showed comparable transduction efficiency (21.4% versus 18.5%, respectively), but BC yielded nearly double the number of viable PBMCs per 50 mL. Upon stimulation and co-culture with target cells, CD4+ SR T cells produced significantly higher levels of IFN-γ, IL-4, and IL-10 compared to CD8+ SR T cells. These cytokines also significantly increased in co-culture supernatants exposed to PD-L1+ cells. No significant differences were found in CD4/CD8 ratios, CD25 expression, or cytokine profiles between PBMC sources. However, BC-derived T cells showed higher apoptosis rates during co-culture.
CONCLUSION AND IMPLICATIONS: BC can be a practical and effective source of PBMCs for T cell engineering. These findings underscore the SR signaling in the activation of CD4+ T cells that may impact the activation of CD8+ T cells, which is essential for effective tumor eradication.