Department of Microbiology, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seoul, 06591, Republic of Korea.
Catholic Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seoul, 06591, Republic of Korea.
BMC Immunol. 2023 Jun 30;24(1):15. doi: 10.1186/s12865-023-00547-2.
CD40L is primarily expressed on activated CD4 T cells and binds to CD40 which is expressed by various cells including dendritic cells, macrophages and B lymphocytes. While CD40-CD40L interaction is known to be direct between B cells and CD4 T cells which results in proliferation and immunoglobulin isotype switching, antigen presenting cells (APCs) were thought to be involved in the delivery of CD4 help to CD8 T cells by cross-talk between CD4 and CD8 T cells and APCs. However, subsequent study demonstrated that CD40L signal can be directly delivered to CD8 T cells by CD40 expression on CD8 T cells. Since most studies have been carried out in murine models, we aimed to investigate the direct effect of CD40L on human peripheral CD8 T cells.
Human peripheral CD8 T cells were isolated to exclude the indirect effect of B cells or dendritic cells. Upon activation, CD40 expression on CD8 T cells was transiently induced and stimulation with artificial APCs expressing CD40L (aAPC-CD40L) increased the number of total and central memory CD8 T cells and also pp65 specific CD8 T cells. Stimulation with aAPC-CD40L also resulted in higher proportion of central memory CD8 T cells.
Our study suggests that CD40L has an effect on the increased number of CD8 T cells through CD40 expressed on activated CD8 T cells and has influence on memory CD8 T cell generation. Our results may provide a new perspective of the effect of CD40L on human peripheral CD8 T cells, which differ according to the memory differentiation status of CD8 T cells.
CD40L 主要表达于激活的 CD4 T 细胞上，并与 CD40 结合，后者表达于包括树突状细胞、巨噬细胞和 B 淋巴细胞在内的各种细胞上。虽然已知 CD40-CD40L 相互作用是 B 细胞和 CD4 T 细胞之间的直接相互作用，导致增殖和免疫球蛋白同种型转换，但抗原呈递细胞（APCs）被认为通过 CD4 和 CD8 T 细胞与 APC 之间的细胞间通讯参与向 CD8 T 细胞提供 CD4 帮助。然而，随后的研究表明，CD40L 信号可以通过 CD8 T 细胞上的 CD40 表达直接传递给 CD8 T 细胞。由于大多数研究都是在鼠模型中进行的，我们旨在研究 CD40L 对人外周血 CD8 T 细胞的直接作用。
分离人外周血 CD8 T 细胞以排除 B 细胞或树突状细胞的间接作用。在激活后，CD8 T 细胞上的 CD40 表达短暂诱导，用表达 CD40L 的人工 APC（aAPC-CD40L）刺激增加了总记忆和中央记忆 CD8 T 细胞的数量，也增加了 pp65 特异性 CD8 T 细胞的数量。用 aAPC-CD40L 刺激也导致中央记忆 CD8 T 细胞的比例更高。
我们的研究表明，CD40L 通过激活的 CD8 T 细胞上表达的 CD40 对 CD8 T 细胞数量的增加有影响，并对记忆 CD8 T 细胞的产生有影响。我们的结果可能为 CD40L 对人外周血 CD8 T 细胞的作用提供一个新的视角，这取决于 CD8 T 细胞的记忆分化状态。
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