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Regulatory T Cells (Tregs) – Function & Importance

Regulatory T cells (Tregs) are specialized immune cells that control the immune system and prevent excessive immune responses. They are essential for avoiding autoimmune diseases.

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Things worth knowing about "Regulatory T cells"

Regulatory T cells (Tregs) are specialized immune cells that control the immune system and prevent excessive immune responses. They are essential for avoiding autoimmune diseases.

What are regulatory T cells?

Regulatory T cells (Tregs) are a specialized subset of T lymphocytes, a type of white blood cell belonging to the adaptive immune system. Their primary role is to regulate and control immune responses, preventing the immune system from attacking the body itself or overreacting to harmless substances such as pollen or food. Tregs are therefore central to maintaining immunological self-tolerance.

Types of regulatory T cells

There are several subgroups of regulatory T cells, differing in their origin and function:

Natural Tregs (nTregs): These develop directly in the thymus and are characterized by expression of the transcription factor FoxP3 and the surface markers CD4 and CD25.
Induced Tregs (iTregs): These arise in peripheral tissues from conventional CD4-positive T cells under the influence of specific cytokines, particularly TGF-beta and IL-2.
Tr1 cells: Another subgroup that produces large amounts of the immunosuppressive cytokine IL-10 and also contributes to immune tolerance.

Mechanism of action

Regulatory T cells suppress the activity of other immune cells through several mechanisms:

Cytokine-mediated suppression: Tregs secrete immunosuppressive mediators such as TGF-beta, IL-10, and IL-35, which inhibit the activation and proliferation of other T cells.
Direct cell contact: Via the molecule CTLA-4, Tregs can block co-stimulatory signals from dendritic cells, thereby preventing the activation of effector T cells.
IL-2 deprivation: Tregs express the high-affinity IL-2 receptor and consume interleukin-2, depriving other immune cells of this essential growth signal.
Cytolysis: In certain situations, Tregs can directly kill other immune cells via granzymes and perforin.

Relevance to health and disease

Autoimmune diseases

A deficiency or dysfunction of regulatory T cells can lead the immune system to attack its own tissues. This plays an important role in the development of autoimmune diseases such as type 1 diabetes, rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus.

Allergies and asthma

Tregs also suppress allergic reactions by inhibiting the activity of Th2 cells and IgE-producing B cells. Reduced Treg activity can contribute to the development of allergies and asthma.

Cancer

In tumor immunology, Tregs play an ambivalent role. They can protect tumors by suppressing the anti-tumor immune response, and elevated Treg numbers within tumors are often associated with a poorer prognosis. Inhibiting Tregs is therefore an important strategy in cancer immunotherapy.

Transplant medicine

In transplant medicine, Tregs may in the future be used to prevent rejection of donor organs and reduce the need for lifelong immunosuppression.

Clinical relevance and research

The targeted manipulation of regulatory T cells is a highly active area of research. Approaches include Treg cell therapy, in which a patient's Tregs are expanded outside the body and then re-infused, as well as drugs that selectively activate or inhibit Tregs. Checkpoint inhibitors used in cancer therapy, such as anti-CTLA-4 antibodies (e.g., ipilimumab), act in part by blocking Treg-mediated suppression. The diagnostic measurement of Treg numbers and function in the blood can provide important insights into the state of the immune system.

References

Sakaguchi, S. et al. (2008): Regulatory T cells and immune tolerance. Cell, 133(5), 775–787. PubMed PMID: 18510923.
Bluestone, J.A., Mackay, C.R., O'Shea, J.J., Stockinger, B. (2009): The functional plasticity of T cell subsets. Nature Reviews Immunology, 9(11), 811–816. PubMed PMID: 19855404.
World Health Organization (WHO): Immunology and vaccine-preventable diseases. Available at: https://www.who.int (accessed 2024).

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