Regulatory T cells, or Tregs, are specialized white blood cells that act as the immune system’s peacekeepers. As a subset of T lymphocytes, they play a fundamental role in regulating immune responses throughout the body. They act as the “brakes” of the immune system, preventing it from overreacting or attacking the body’s own healthy tissues. Without Tregs, the immune system could become overly aggressive, leading to unintended harm.
The Primary Function of Regulatory T Cells
The main purpose of regulatory T cells is to maintain immune balance, also known as immune homeostasis. This involves ensuring the immune system can effectively identify and eliminate foreign invaders like bacteria and viruses, while simultaneously distinguishing between these threats and the body’s own “self” cells. This ability to recognize and tolerate self-components is termed self-tolerance.
Tregs are crucial for preventing the immune system from mistakenly attacking healthy tissues and organs, a process that would lead to autoimmune diseases. Beyond preventing self-attack, they also play a role in winding down an immune response once an infection has been successfully cleared. This controlled de-escalation prevents unnecessary inflammation and collateral damage after the threat has been neutralized.
Mechanisms of Immune Suppression
Regulatory T cells employ several precise mechanisms to carry out their suppressive functions. One method involves releasing specific signaling molecules known as cytokines, such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta). These cytokines act as calming signals, instructing other immune cells to reduce their activity and proliferation.
Tregs can also directly interact with other immune cells through surface proteins. For instance, they express cytotoxic T-lymphocyte antigen 4 (CTLA-4), which can bind to molecules on antigen-presenting cells, effectively delivering a “stop” signal that dampens the activation of other T cells. Additionally, Tregs can deplete local growth factors like interleukin-2 (IL-2) by expressing high levels of its receptor, CD25, thereby starving other immune cells that need IL-2 to function. This competition for resources further limits the activity of immune responses.
Tregs and Autoimmune Disorders
When the delicate balance maintained by regulatory T cells is disrupted, either due to insufficient numbers or impaired function, the immune system’s brakes can fail. This leads to autoimmune disorders, conditions where the immune system erroneously targets and damages the body’s own healthy tissues. The transcription factor FOXP3 is particularly important for Treg development and function; mutations in the FOXP3 gene can lead to severe autoimmune conditions like IPEX syndrome.
A reduction in Treg frequency or a decline in their suppressive activity is a consistent finding in many autoimmune diseases. For example, in Type 1 diabetes, the immune system attacks insulin-producing cells in the pancreas, and patients often show a reduced number of functional Tregs. Similarly, in rheumatoid arthritis, the immune system attacks joint tissues, and in multiple sclerosis, it targets the protective sheaths around nerve fibers, with Treg dysfunction contributing to these attacks. Other conditions linked to Treg deficiencies include lupus and inflammatory bowel disease.
The Role of Tregs in Cancer Progression
The same immunosuppressive function that protects against autoimmunity can become detrimental in the context of cancer. Tumors often exploit regulatory T cells to evade detection and destruction by the immune system. Cancer cells can actively recruit Tregs to the tumor microenvironment, creating a protective shield around themselves.
Once recruited, these tumor-associated Tregs suppress anti-cancer immune cells, such as killer T cells and natural killer (NK) cells, which would normally recognize and eliminate malignant cells. This suppression allows the tumor to grow unchecked and potentially metastasize. High levels of Tregs infiltrating tumors have been associated with poor patient prognosis in various cancers, including breast, gastric, and pancreatic cancers.
Therapeutic Manipulation of Tregs
Scientists are actively exploring ways to manipulate regulatory T cells for therapeutic benefit, either by boosting their activity in autoimmune conditions or inhibiting them in cancer. For autoimmune diseases, the goal is to enhance Treg numbers or function to restore immune balance. One promising approach is adoptive Treg therapy, which involves isolating a patient’s own Tregs, expanding them in the laboratory, and then reinfusing them back into the patient. This method aims to provide a targeted, antigen-specific suppression of the autoimmune response without broadly suppressing the entire immune system.
Conversely, in cancer treatment, therapies aim to block or deplete Tregs within the tumor microenvironment. This strategy seeks to “release the brakes” on the anti-cancer immune response, allowing effector immune cells to more effectively attack and destroy tumor cells. Approaches include using antibodies that target specific Treg markers like CD25, or combining Treg depletion with other immunotherapies, such as checkpoint inhibitors, to enhance the overall anti-tumor effect.