The immune system has cells that control its responses, preventing damage to the body’s own tissues. Among these are Type 1 regulatory T cells (Tr1 cells), which help ensure defensive actions are directed only against genuine threats. This function is important for preventing inappropriate inflammation and maintaining immune health.
The Core Function of Tr1 Cells
The primary role of Tr1 cells is to maintain immune tolerance, a state where the immune system does not react to harmless substances or its own tissues. They are defined by their capacity to produce large quantities of the signaling molecule Interleukin-10 (IL-10). This anti-inflammatory cytokine serves as a “stand down” signal to other, more aggressive immune cells.
When Tr1 cells release IL-10, it inhibits the activation and function of effector T cells, which are responsible for directly attacking pathogens or infected cells. This prevents these aggressive cells from causing collateral damage to healthy tissues and helps resolve inflammation once a threat is neutralized.
Beyond IL-10, Tr1 cells employ other mechanisms to control immune responses. They produce another suppressive molecule, Transforming Growth Factor-beta (TGF-β). They can also directly kill the antigen-presenting cells that initiate immune responses through the release of substances like Granzyme B.
How Tr1 Cells Are Created
Tr1 cells are not a predetermined lineage that develops in a central location like the thymus. Instead, they are induced in the periphery from common T cells when specific environmental cues are present. This process begins with a naive T helper cell, which can become various types of specialized T cells.
The transformation is triggered when a naive T cell encounters a persistent antigen in a specific biochemical environment. A signal in this process is the presence of IL-10 itself. When naive T cells are repeatedly stimulated in an IL-10-rich environment, they are programmed to differentiate into Tr1 cells.
Other factors also guide this differentiation. Tolerogenic dendritic cells play a part by presenting antigens in a non-inflammatory context. Cytokines like IL-27 also promote the generation of Tr1 cells from naive precursors.
Differentiating Tr1 Cells from Other T Cells
The most notable comparison for Tr1 cells is with another group of regulatory T cells known as Foxp3+ Tregs. While both cell types are suppressive, they have distinct origins and identifying features. The defining characteristic of conventional Tregs is the presence of a regulatory protein called Foxp3, which Tr1 cells lack.
Tr1 cells are primarily identified by their high production of IL-10, which is their functional signature. This distinction in origin and markers suggests they have different, though sometimes overlapping, roles in regulating immunity.
In contrast to regulatory cells, effector T cells like Th1 and Th17 cells are designed to be aggressive attackers. Tr1 cells act as a counterbalance to these cells, with their IL-10 production directly suppressing the inflammatory activities of Th1 and Th17 cells.
The Role of Tr1 Cells in Disease and Health
In autoimmune diseases, where the immune system mistakenly attacks its own tissues, Tr1 cells play a protective role. For conditions like inflammatory bowel disease (IBD) and multiple sclerosis, Tr1 cells help suppress the self-reactive immune cells that drive the disease, reducing inflammation and tissue damage.
Tr1 cells are also beneficial in organ transplantation. They contribute to establishing tolerance to the transplanted organ by dampening the aggressive immune response directed against it. In allergic reactions, where the immune system overreacts to harmless substances, Tr1 cells can help control the inflammatory cascade.
The suppressive nature of Tr1 cells can be disadvantageous in certain situations. In cancer, Tr1 cells may inadvertently protect tumors from immune attack by suppressing T cell activity. This can create an environment where cancer cells can grow unchecked.
Therapeutic Potential of Tr1 Cells
The ability of Tr1 cells to suppress unwanted immune responses has made them a focus of therapeutic research. Scientists are exploring “cell therapy,” which involves growing Tr1 cells in a laboratory and then infusing them into a patient to restore immune balance.
This therapy holds promise for treating autoimmune diseases. By introducing a large population of Tr1 cells, it may be possible to calm the misdirected immune attacks that characterize conditions like Crohn’s disease or lupus. The infused cells could migrate to sites of inflammation and suppress the cells causing the damage.
In organ transplantation, Tr1 cell therapy is being investigated to promote long-term graft survival and reduce the need for powerful immunosuppressive drugs. By generating Tr1 cells that are specific to the donor organ’s antigens, it may be possible to induce tolerance, teaching the recipient’s immune system to accept the transplant.