The immune system relies on a complex communication network between cells to protect the body. This communication is managed by proteins on cell surfaces that act as identification markers and signaling devices. One such protein, Cluster of Differentiation 80 (CD80), serves as a point of contact that influences how the immune system responds.
Understanding CD80 and Its Role on Immune Cells
CD80 is a protein on the surface of specific immune cells and is a member of the immunoglobulin superfamily. Its primary function is to interact with T cells of the adaptive immune system. The presence of CD80 provides a signal that can initiate or suppress immune activity depending on the interaction’s context.
This marker is not found on all cells but is expressed on antigen-presenting cells (APCs). These specialized cells include dendritic cells, macrophages, and B cells. Their job is to process foreign materials, like viruses or bacteria, and display fragments of them—called antigens—to T cells to initiate a targeted immune response.
The expression of CD80 on these APCs is not constant, as it increases significantly when the cells detect infection or inflammation. This alerts the immune system that a response is needed. While associated with APCs, CD80 can also be found on activated T cells and B cells, suggesting a broader role in immune communication.
How CD80 Signals and Activates the Immune System
T cell activation is a tightly controlled process that requires more than just the recognition of a foreign antigen. A second, confirming signal is needed for full activation, a concept known as the “two-signal hypothesis.” CD80 is a primary provider of this second signal.
When an antigen-presenting cell (APC) displays an antigen to a T cell, CD80 on the APC’s surface binds to a protein on the T cell called CD28. This CD80-CD28 interaction delivers the co-stimulatory signal that promotes T cell survival, proliferation, and the production of cytokines. This ensures that T cells mount a sustained attack against the identified threat.
CD80’s role is not limited to activating immune responses. It can also bind to a different T cell receptor called Cytotoxic T-Lymphocyte-Associated protein 4 (CTLA-4). Unlike CD28, CTLA-4 is an inhibitory receptor. When CD80 binds to CTLA-4, it sends a signal that dampens the T cell’s activity.
This dual-receptor system allows for precise control over the immune system. The activating CD80-CD28 link helps initiate a defense, while the inhibiting CD80-CTLA-4 connection helps shut down the response once the threat is neutralized. This inhibitory function is also important for maintaining self-tolerance, which prevents the immune system from attacking the body’s own healthy tissues.
CD80’s Involvement in Disease
The regulatory function of CD80 means that dysregulated signaling can contribute to various diseases. A disruption in the balance between its stimulatory and inhibitory signals can lead to either an overactive or an underactive immune response.
In autoimmune diseases, the immune system mistakenly attacks the body’s own tissues. Overexpression or persistent signaling through the CD80-CD28 pathway can contribute to this by providing excessive co-stimulation to self-reactive T cells. This lowers the threshold for T cell activation, allowing them to attack healthy tissues. Conditions like multiple sclerosis are linked to more circulating immune cells expressing CD80.
Conversely, an insufficient CD80 signal can hinder the body’s ability to fight tumor cells. T cells need strong activation signals to be effective. If tumor cells or surrounding APCs fail to express adequate CD80, T cells may not receive the necessary co-stimulation, leading to a state of inactivation known as anergy.
The CD80 pathway is also a factor in organ transplant rejection. A recipient’s immune system recognizes the donor organ’s cells as foreign. CD80 expressed on the recipient’s APCs or the donor organ’s cells can activate the recipient’s T cells through the CD28 receptor. This triggers an immune response directed at the transplanted organ.
Targeting CD80 in Medical Treatments
Understanding CD80’s function has led to targeted medical therapies. By modulating its signals, it is possible to suppress an unwanted immune response or enhance a desirable one. These treatments often focus on blocking or mimicking the interactions between CD80 and its binding partners.
A prominent strategy for treating autoimmune diseases and preventing transplant rejection involves blocking the CD80-CD28 co-stimulatory signal. This is achieved with drugs known as CTLA-4-Ig fusion proteins, such as abatacept and belatacept. These engineered molecules combine the CD80-binding portion of CTLA-4 with an antibody fragment. They work by binding to CD80 and its relative, CD86, on APCs, preventing them from interacting with CD28 on T cells.
This blockade calms an overactive immune system in autoimmune conditions and prevents T cells from attacking a transplanted organ. In cancer immunotherapy, the focus is on boosting the immune response. While not always targeting CD80 directly, therapies like checkpoint inhibitors that block CTLA-4 or PD-1 disrupt the inhibitory signals restraining T cells. By blocking these brakes, activating signals from CD80-CD28 have a more dominant effect, allowing T cells to attack tumors.