BackgroundCD40L 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.ResultsHuman 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.ConclusionsOur 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.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12865-023-00547-2.