Within the immune system, a specialized group of white blood cells known as regulatory T cells, or Tregs, function as peacekeepers. Their primary role is to modulate the body’s immune responses, preventing them from becoming excessive or misdirected. An immune response requires an off-switch, as without this control the immune system could turn against the body’s own tissues. Tregs provide this braking mechanism, ensuring that immune reactions are restrained when a threat has passed to maintain a state of equilibrium known as homeostasis.
The Role of Immune System Peacekeepers
Regulatory T cells are fundamental to establishing and maintaining immune tolerance, which is the body’s ability to recognize its own cells and tissues as “self.” This process of self-tolerance is a continuous responsibility managed by Tregs, which patrol the body to prevent self-reactive immune cells from causing damage. After the immune system clears an infection, Tregs suppress the remaining activated immune cells. This action is important for preventing chronic inflammation, a state that can cause progressive damage to tissues over time.
The role of Tregs also extends to tolerating beneficial foreign entities, such as the communities of microbes that reside in the gut. These bacteria are not part of the human body, yet they provide many benefits. Tregs help to manage the immune response in the gut, preventing a constant state of inflammation that would otherwise be directed at these helpful residents.
Mechanisms of Suppression
Regulatory T cells employ a variety of strategies to suppress the activity of other immune cells. One of their primary methods is the secretion of anti-inflammatory signaling molecules, known as cytokines. Two of the most important of these are Interleukin-10 (IL-10) and Transforming Growth Factor-beta (TGF-beta). These molecules act as chemical messengers that instruct other immune cells to stand down.
Another tactic involves direct cell-to-cell contact. Tregs can physically interact with other immune cells, such as T helper cells, and deliver inhibitory signals directly. This contact-dependent suppression is a targeted way of ensuring that specific, potentially harmful immune cells are deactivated, without shutting down the entire immune system.
Tregs also act as a “resource sink,” starving other immune cells of the resources they need to multiply and sustain an attack. They are characterized by a high expression of a surface marker called CD25, which is part of the receptor for a growth factor called Interleukin-2 (IL-2). By absorbing large amounts of IL-2, Tregs deprive other T cells of this substance, which they need to proliferate.
When Balance Is Lost
The balance maintained by regulatory T cells is indispensable for health, and any disruption can have significant consequences. When Treg activity is insufficient, the immune system’s brakes fail, and it can begin to attack the body’s own tissues. This loss of self-tolerance is the underlying cause of autoimmune diseases, where the immune system misidentifies healthy cells as foreign invaders and launches a sustained assault against them.
Conditions such as Type 1 diabetes, where the immune system destroys insulin-producing cells in the pancreas, and multiple sclerosis, where the protective covering of nerves is targeted, are examples of this imbalance. Similarly, rheumatoid arthritis, which involves the immune system attacking the joints, stems from a failure of Tregs to properly restrain the immune response. Allergies and asthma are also linked to insufficient Treg function.
Conversely, an excess of Treg activity can also be detrimental, particularly in the context of cancer. Many tumors have developed the ability to exploit the suppressive power of Tregs to protect themselves from the immune system. These cancers can actively recruit Tregs to the tumor site, creating a localized environment of immune suppression. This “protective shield” prevents cancer-fighting immune cells from recognizing and destroying the malignant cells, allowing the tumor to grow and spread unchecked.
Therapeutic Applications
Understanding the dual role of regulatory T cells in health and disease has opened new avenues for medical treatments. Researchers are developing therapies that aim to manipulate Treg populations to restore immune balance. These strategies are divided into two main approaches: either boosting Treg activity or inhibiting it, depending on the specific disease being targeted.
For autoimmune diseases, where the problem is an under-regulated immune system, the goal is to enhance Treg function. One strategy involves isolating a patient’s own Tregs, expanding their numbers in a laboratory, and then reinfusing them back into the body. This approach, known as adoptive Treg therapy, aims to bolster the body’s natural peacekeeping force. This method is also being explored to help prevent the rejection of transplanted organs.
In cancer treatment, the objective is the opposite: to inhibit Treg activity to unleash the immune system’s power against tumors. Many cancer immunotherapies, such as checkpoint inhibitors, work in part by blocking the suppressive signals that Tregs use. These drugs allow cancer-fighting cells to recognize and attack tumor cells that were previously protected.