Expression of CD80 on Kupffer cells is enhanced in cadaveric liver transplants

Abstract

SUMMARYIn experimental animals inhibition of T cell co-stimulation immediately after organ transplantation effectively prevents rejection. We investigated whether the expression of co-stimulatory molecules is enhanced in cadaveric liver transplants, whether their expression is influenced by the transplantation procedure, and whether variation in expression between liver transplants is related to the occurrence of acute rejection. Expression of CD80, CD86 and the macrophage marker CD68 were determined by immunohistochemistry in biopsies from 40 clinical liver transplants obtained at different time-points during the transplantation procedure, and in normal liver tissue obtained from 10 human livers. Expression of CD80 and CD86 on Kupffer cells was graded by comparison with CD68-staining. In a subgroup CD80 and CD86 mRNA was quantified by real-time detection polymerase chain reaction. CD86 was expressed in all liver transplants and normal livers on the majority of Kupffer cells. CD80 was absent or sporadically expressed in normal liver tissue, but in 18 of 40 liver transplants at least one-quarter of Kupffer cells expressed CD80. CD80-and CD86-mRNA and protein expression in liver transplants did not change during the warm ischaemic and reperfusion phases of the transplantation procedure. CD80-expression on Kupffer cells varied strongly between individual donor livers; this variation was, however, not significantly related to the occurrence of acute rejection after transplantation. In conclusion, in nearly half of cold-preserved cadaveric liver transplants an increased proportion of Kupffer cells express CD80 at the time of transplantation in comparison with normal liver tissue. The expression was not further induced by warm ischaemia and reperfusion. However, the observed variation in CD80-expression between liver transplants is not a accurate predictive measure for acute rejection.

The immunophenotype of antigen presenting cells of the mononuclear phagocyte system in normal human liver – A systematic review

“…However, KCs appear to be heavily involved in both the innate and the acquired immune responses within the liver. KCs express MHC class II, and express varying levels of co-stimulation markers (such as CD40, CD80, and CD86 [77]), as well as the inhibitory markers such as Z39Ig [89]. In the steady state they act as sentinel scavenging cells to process antigen from the gut.…”

“…• "Thin"-extended cytoplasm [32] • "Round"-larger cells with round cytoplasm [32] • 5 subsets defined by varying endogenous peroxidase activity and levels of endoplasmic reticulum [86] • Minimal functional experimental evidence on liver macrophages • Liver Macrophages appear to be predominantly tolerogenic in nature, with a regulatory and scavenging role [41,57,69,89] • Function inferred through observations of variable expression of antigen presenting molecules [72], lectins [33,49,55,69,92], Fc Receptors, complement receptors [70], low co-stimulatory marker expression [77] and inhibitory markers such as Z39Ig [89] Perisinusoidal [78] • [101] Tolerogenic in nature • Lower expression of costimulation markers compared to spleen [98] • Produce IL-10 on LPS stimulation [98] • Stimulate T-cells that are IL-10 producing and hypo-responsive on re-stimulation [98] • Produce higher numbers of FoxP3 + Treg cells on naïve T cell stimulation [98] • Weak MLR response compared to blood [98] Portal tract [103] • divided into subsets with different potential for antigen presentation, motility, and cytokine production, all of which can help determine the nature of the immune system's response [17]. A particular complicating factor in the case of the liver is that circulating monocytes also traffic through the sinusoids, and distinguishing between in transit monocyte subsets and other MPS subsets is an evolving science [17].…”

Lack of gp130 expression results in more bacterial infection and higher mortality during chronic cholestasis in mice

“…This staining is selective for Kupffer cells. 17 To quantitate immunostained positive cells accurately, slides were viewed by digital microscopy (Axioplan 2, Carl Zeiss, Oberkochen, Germany). Digital pictures were captured through a video archival system using a digital TV camera system (Axiocam High Resolution color, Carl Zeiss).…”

Immunology of Liver Transplantation

“…In addition, ligands for CD28, including B7-1 (CD80) and B7-2 (CD86), are present on various antigen-presenting cells including dendritic cells, B cells, and macrophages. 21 The CD80 antigen is expressed only sporadically on normal liver cells but may be present on 25% Kupffer cells in 45% transplanted livers. The CD86 antigen is observed on most Kupffer cells in all transplanted liver and normal liver tissue.…”