CD80 can be found on the surface of various immune cells including B cells, monocytes and antigen-presenting cells such as dendritic cells and is the receptor for the proteins CD28 and CTLA-4 found on the surface of T-cells. CD80 binds to CD28 and CTLA-4 with lower affinity and fast binding kinetics, allowing for quick interactions between the communicating cells. This interaction results in an important costimulatory signal in the immunological synapse between antigen-presenting cells, B-cells, dendritic cells and T-cells that result in T and B-cell activation, proliferation and differentiation. CD80 is an especially important component in dendritic cell licensing and cytotoxic T-cell activation. When the major histocompatibility complex class II - peptide complex on a dendritic cell interacts with the receptor on a T helper cell, CD80 is up-regulated, licensing the dendritic cell and allowing for interaction between the dendritic cell and CD 8+ T-cells via CD28. This helps to signal the T-cell differentiation into a cytotoxic T-cell. CD80, often in tandem with CD86, plays a large and diverse role in the regulation of both the adaptive and the innate immune system. As mentioned above, this protein is very important for immune cell activation in response to pathogens. This activation occurs through stimulatory interaction with CD28, which can enhance cytokine production, and cell proliferation, and prevent apoptosis. CD80 interaction with CD28 also further stimulates dendritic cells, again enhancing cytokine production, specifically IL-6, a proinflammatory molecule. Neutrophils can also activate macrophages with CD80 viaCD28. In contrast to the stimulatory interaction with CD28, CD80 also regulates the immune system through an inhibitory interaction with CTLA-4. Dendritic cells have been found to be suppressed by a CTLA-4-CD80 interaction and this interaction also promotes the suppressive effects of regulatory T cells, which can prevent an immune response to self-antigen. In addition to interactions with CD28 and CTLA-4, CD80 is also thought to interact with a separate ligand on Natural Killer cells, triggering the Natural Killer cell-mediated cell death of the CD80 carrier. CD80 may also play a role in the negative regulation of effector and memory T-cells. If the interaction between an antigen-presenting cell and a T-cell is stable enough, the T-cell can remove the CD80 from the antigen-presenting cell. Under the right conditions, this transfer of the CD80 may induce T-cell apoptosis. Finally, CD80 signaling on activated B-cells may regulate antibody secretion during infection.
Clinical significance
The complicated role CD80 plays in immune system regulation presents an opportunity for CD80 interactions to go rogue in various diseases. The up-regulation of CD80 has been linked to various autoimmune diseases, including multiple sclerosis, systemic lupus erythematosus and sepsis, and CD80 has also been shown to help spread of HIV infection in the body. CD80 is also linked to various cancers, though some experience CD80 induced tolerance via possible regulatory T cell interaction and others experience inhibited growth and metastasis related to CD80 up-regulation, further exemplifying the complicated role CD80 plays. The triggering of Natural Killer cell-mediated death via CD80 interactions has been explored as a possible cancer immunotherapy, through the induction of CD80 expression on tumor cells. Some therapies for autoimmune diseases involve the down-regulation of CD80, including the use of the immunosuppressants, resveratrol found in red grapes and curcumin found in turmeric.
