CD134 is a protein on the surface of activated T cells and a member of the tumor necrosis factor receptor superfamily. Also known as OX40 or TNFRSF4, this receptor is not present on resting T cells. Its appearance on the cell surface is a signal that an immune response is underway.
Function in the Immune System
As a co-stimulatory molecule, CD134 provides a secondary signal that amplifies an immune response. This process starts when CD134 on an activated T cell binds to its partner, the CD134 ligand (or OX40L). This ligand is found on antigen-presenting cells, which initially show the threat to the T cell. The interaction is like needing a second key to start an engine; the first key turns it on, but the second provides the power to move forward.
This binding event promotes the survival of activated T cells and encourages them to multiply. The sustained signaling also helps T cells mature into memory T cells, which persist long after an infection is cleared. Should the same pathogen enter the body again, these memory T cells mount a much faster defense, a process fundamental to how vaccines protect against diseases.
Role in Autoimmune Disorders
While beneficial for fighting infections, the boosting signal from the CD134 pathway can be detrimental if unregulated. If the signaling is too strong or persistent, it can drive T cells to become overactive. This causes the immune system to lose its ability to distinguish between foreign invaders and the body’s own tissues, leading T cells to attack the body itself, the underlying cause of autoimmune diseases.
This damaging mechanism is observed in conditions like rheumatoid arthritis, where T cells contribute to joint destruction, and multiple sclerosis, where they attack nerve fibers. In systemic lupus erythematosus, T cell hyperactivity leads to widespread organ damage. In these diseases, the CD134 molecule is often found in high numbers at sites of inflammation, making the pathway a target for therapies aimed at dampening the immune response.
Significance in Cancer Treatment
In cancer treatment, the goal is the opposite of that for autoimmune disorders; the immune system needs to be more aggressive. Cancer cells can create a suppressive environment that weakens T cell activity, allowing tumors to grow. Manipulating the CD134 pathway is a strategy in immunotherapy to reinvigorate the body’s defenses against malignant cells.
Therapies using drugs known as “CD134 agonists” mimic the natural ligand to artificially activate the receptor on T cells. This provides a “go” signal that overcomes the suppressive effects of the tumor environment. The stimulated T cells are then better equipped to recognize and kill cancer cells.
This approach enhances the T cells’ ability to mount a sustained attack and generate a memory response against the cancer. These agonist drugs are often investigated in combination with other immunotherapies to create a more comprehensive anti-cancer effect.
Therapeutic Targeting Beyond Cancer
The ability to block the CD134 pathway also makes it a target for other conditions. Inhibiting the signal with drugs called “antagonists” is a strategy for conditions driven by an undesirable T-cell response where the immune system causes harm.
One example is graft-versus-host disease (GVHD), a complication of bone marrow or stem cell transplants. In GVHD, the donor’s immune cells attack the recipient’s body. Blocking CD134 signaling can calm these donor T cells and reduce the disease’s severity.
This principle of inhibition also applies to severe allergic reactions and asthma, which involve an overactive T-cell response to harmless substances. Blocking the CD134 pathway could reduce the T-cell activity that drives chronic inflammation in the airways of asthma patients.