Expression of the Murine CD27 Ligand CD70 In Vitro and In Vivo

Abstract

The interaction between TNFR family member CD27 and its ligand CD70 promotes lymphocyte expansion and effector cell formation. In humans, control of CD27 function is partly regulated by the restricted expression of CD70. We used newly developed mAbs to characterize murine (m) CD70 expression in vitro and in vivo. On resting lymphocytes and immature dendritic cells (DC), mCD70 is absent. In vitro, Ag receptor triggering induced mCD70 mRNA in T cells, but cell surface protein expression was very low. Activated B cells synthesized much higher levels of mCD70 mRNA than activated T cells and clearly expressed mCD70 at the cell surface. mCD70 cell surface expression could also be induced on the DC line D1 and on in vitro-generated murine DC upon maturation. In lymphoid organs of naive mice, virtually no mCD70-expressing cells were found, with exception of cells in the thymic medulla, which may be epithelial in origin. However, after intranasal infection with influenza virus, lung-infiltrating T cells and T and B cells in draining lymph nodes expressed mCD70 according to immunohistology. In such activated lymphocytes, mCD70 protein is largely retained intracellularly. Plasma membrane expression of mCD70 was only detectable by flow cytometry on a small proportion of lung-infiltrating T cells and peaked at the height of the primary response. Thus, expression of CD70 in the mouse is highly regulated at the transcriptional and posttranslational level. This most likely serves to limit excessive effector cell formation after antigenic stimulation.

Properties of murine CD8+CD27- T cells

“…CD27 down modulation is limited to a small percentage of T cells late after primary influenza infection but is much more pronounced late after secondary influenza infection. After influenza virus infection, CD70 expression could be found on infrequent T and B cells in DrLN and some lung-infiltrating T cells [48]. Thus after primary influenza infection, CD27 on activated CD8 + T cells might be triggered in DrLN by CD70 expressed on activated immune cells.…”

“…This might be explained by differences in the frequency of antigen (re)encounter or potentially in the amount of CD70 expressed and the localization of CD70-expressing cells. The tropism of CMV at latent stage is mainly confined to endothelial cells and monocytes [47] that might induce continuous immune activation and CD70 expression on activated T and B cells at local sites while influenza infection might cause only transient CD70 expression because it is believed to be completely eradicated from the host [48]. CD27 down modulation is limited to a small percentage of T cells late after primary influenza infection but is much more pronounced late after secondary influenza infection.…”

CD70 (TNFSF7) is expressed at high prevalence in renal cell carcinomas and is rapidly internalised on antibody binding

“…To compare expression of CD70 with CA9, we performed real-time quantitative RT -PCR analysis on multiple normal tissues and clinical RCC samples (Figure 7). These data showed that there was no detectable CD70 mRNA in any of the 29 normal tissues examined; in the thymus, reported expression of CD70 in the medullary epithelium (Hintzen et al, 1994;Tesselaar et al, 2003) was likely diluted below the limit of detection by the presence in this tissue of other, non-expressing cell types. In contrast, there were high levels of CA9 in the stomach and testis, and to a lesser extent in the small intestine and prostate.…”

Late Signals from CD27 Prevent Fas-Dependent Apoptosis of Primary CD8+ T Cells

“…CD27 down-regulation results from decreased transcription (19) and proteolytic cleavage of membrane bound CD27 and gives rise to soluble CD27, which can be used as an indication of T cell activation (22). CD27L is transiently expressed on activated T and B cells upon Ag receptor engagement as well as some dendritic cells (DC) 3 (23,24). Activated T cells up-regulate CD27L and can directly stimulate naive T cells through CD27, which causes downregulation of CD27 and up-regulation of CD25 (25).…”