The Analysis of CD83 Expression on Human Immune Cells Identifies a Unique CD83+-Activated T Cell Population

Abstract

CD83 is a member of the Ig gene superfamily, first identified in activated lymphocytes. Since then, CD83 has become an important marker for defining activated human dendritic cells (DC). Several potential CD83 mRNA isoforms have been described, including a soluble form detected in human serum, which may have an immunosuppressive function. To further understand the biology of CD83, we examined its expression in different human immune cell types before and after activation using a panel of mouse and human anti-human CD83 mAb. The mouse anti-human CD83 mAbs, HB15a and HB15e, and the human anti-human CD83 mAb, 3C12C, were selected to examine cytoplasmic and surface CD83 expression, based on their different binding characteristics. Glycosylation of CD83, the CD83 mRNA isoforms, and soluble CD83 released differed among blood DC, monocytes, and monocyte-derived DC, and other immune cell types. A small T cell population expressing surface CD83 was identified upon T cell stimulation and during allogeneic MLR. This subpopulation appeared specifically during viral Ag challenge. We did not observe human CD83 on unstimulated human natural regulatory T cells (Treg), in contrast to reports describing expression of CD83 on mouse Treg. CD83 expression was increased on CD4, CD8 T, and Treg cells in association with clinical acute graft-versus-host disease in allogeneic hematopoietic cell transplant recipients. The differential expression and function of CD83 on human immune cells reveal potential new roles for this molecule as a target of therapeutic manipulation in transplantation, inflammation, and autoimmune diseases.

Genome-wide association studies for tick resistance in Bos taurus × Bos indicus crossbred cattle: A deeper look into this intricate mechanism

“…Gene CD83 is expressed in most immune cells such as B cells (Kretschmer et al, 2007), monocytes and macrophages (Cao et al, 2005), neutrophils (Yamashiro et al, 2000), and a regulatory subset of natural killers cells (Mailliard et al, 2005), thus showing its essential role in the initiation and regulation of innate and adaptive immune responses. It acts in the stimulation of immature and memory T cells by activation of DC (Aerts-Toegaert et al, 2007), thymic maturation and activation of CD4 + and CD8 + (Ju et al, 2016), maturation and maintenance of peripheral lymphocyte B homeostasis (Lüthje et al, 2008), and in the increased expression of MHC class I and CD86 (Tze et al, 2011). Thus, this gene also has functions potentially involved with the physiological response to tick infestation in cattle, what makes it a candidate gene for this trait along with TREM1 and TREM2.…”

Heritability and family-based GWAS analyses of the N-acyl ethanolamine and ceramide plasma lipidome

“…CER[N(26)S(19)] associated at GWAS with SNPs at a novel locus on chromosome 6, upstream to the gene encoding the inflammatory protein CD83 (P=2.07×10 -8 ), a member of the immunoglobulin superfamily of membrane receptors expressed by antigen-presenting white blood cells, leukocytes, and dendritic cells 49 . An interaction between CD83 and CER is currently unknown, but given the involvement of ceramide signalling in inflammation and immunity 50,51 , it would be of interest to investigate further.…”

The CD83 Molecule – An Important Immune Checkpoint

“…This notion is reinforced by the fact that many cell types, which have been reported to bind sCD83, indeed express mbCD83. For instance, binding of sCD83 to human T cells required their prior activation using agonistic anti-CD3/CD28 antibodies (65), a treatment that also induces mbCD83 expression (62). Additionally, the model of homotypic interaction integrates both the immune-regulatory effects of sCD83 and immunomodulatory function of mbCD83: if one interaction partner is missing, immune responses are more likely to derail.…”