CD83 plays a role in the body’s immune system. It is a protein found on the surface of various immune cells, acting as a communicator and regulator. Understanding CD83 helps explain how the body defends itself and maintains immune balance.
Understanding CD83
CD83 is a protein primarily located on the surface of certain immune cells, and it also exists in a soluble form circulating in the body. As a member of the immunoglobulin (Ig) superfamily, its structure includes an extracellular, a transmembrane, and an intracellular domain. It is an activation marker on the surface of activated immune cells.
CD83 is most highly expressed by mature dendritic cells (DCs). However, it can also be found on other activated hematopoietic cells, including B cells, macrophages, monocytes, neutrophils, and natural killer (NK) cells. While present on activated T cells, its expression levels are generally lower than on dendritic cells.
CD83’s Role in Immune Cell Communication
CD83 participates in communication between immune cells, especially in antigen presentation, where immune cells “show” foreign invaders to others. Dendritic cells, as antigen-presenting cells, mature upon encountering foreign substances and migrate to lymph nodes. There, they express cell surface molecules, including CD83, to bind and stimulate T cells, initiating an immune response.
The presence of membrane-bound CD83 (mCD83) on dendritic cells generally promotes their maturation and ability to activate T cells effectively. Reducing CD83 expression on mature dendritic cells impairs their capacity to stimulate T cells in laboratory settings. Conversely, increasing CD83 expression on immature and mature dendritic cells can enhance their T cell stimulatory capacity.
CD83 and Immune System Balance
CD83 plays a role in regulating and fine-tuning immune responses, helping to prevent the immune system from overreacting or attacking healthy tissues. It is considered an important immune checkpoint molecule that contributes to resolving inflammation. Both its membrane-bound and soluble forms are involved.
Membrane-bound CD83 on dendritic cells and regulatory T cells helps control inflammatory responses by inducing regulatory mechanisms. Soluble CD83 (sCD83) can also induce resolution of inflammation in autoimmune conditions and promote tolerance after organ transplantation. Animals with CD83 deletion in their dendritic cells or regulatory T cells experience impaired resolution of inflammation, demonstrating CD83’s role in immune balance.
CD83’s Impact on Disease
Alterations in CD83 expression or function are linked to various diseases, including autoimmune conditions, cancer, and infectious diseases. In autoimmune conditions like rheumatoid arthritis, the immune system mistakenly attacks the body’s own tissues. CD83’s ability to induce regulatory mechanisms, such as promoting regulatory T cells and tolerogenic dendritic cells, is significant in addressing these diseases.
In cancer, CD83 plays a role in how tumors evade immune detection or suppress immune responses. For example, Hodgkin lymphoma cells can express membrane CD83 and secrete soluble CD83, which can inhibit T cell proliferation. In infectious diseases, CD83 on dendritic cells influences the host’s immune response against bacteria, as CD83-deficient dendritic cells show altered responses.
CD83 in Medicine
CD83 is relevant in medical contexts, both as a biomarker and a therapeutic target. Soluble CD83 levels in the blood can be elevated in patients with autoimmune diseases and certain blood cancers, suggesting its potential as a diagnostic or monitoring tool. For instance, high levels of soluble CD83 have been detected in Hodgkin lymphoma patients, returning to normal in those who respond well to chemotherapy.
As a therapeutic target, manipulating CD83 activity could offer strategies for treating various conditions. Drugs designed to inhibit CD83 could dampen an overactive immune system in autoimmune diseases like rheumatoid arthritis, multiple sclerosis, or lupus. Conversely, enhancing CD83 activity or administering recombinant soluble CD83 has shown potential to induce immune tolerance, prevent transplant rejection, or alleviate autoimmune symptoms.