The Secrets of Regulatory T Cells: Balancing Immunity and Health

Updated on Mar 7, 2024 Share

T cells are known as the guardians of our immune system, initiating and maintaining our defense against infections and diseases. While there are many types of T cells, regulatory T cells, or Tregs, have the unique ability to keep balance in the immune system.

Tregs help ensure that our bodies react effectively against pathogens while preventing excessive or misdirected immune responses that can lead to autoimmune diseases. Tregs serve as moderators, preventing our immune system from overactivating and mistakenly attacking our own cells.

What Is a Regulatory T cell?

A regulatory T cell (Treg) is a specialized T cell subset that regulates the immune system, maintaining homeostasis and self-tolerance. They are characterized by the expression of CD4 and CD25 surface markers and the transcription factor FOXP3, which is critical to their development and function.

Understanding the origins and mechanisms of these cells allows scientists to research new ways to maintain immune homeostasis and create potential therapeutics for various diseases.

What Differentiates a Treg?

Regulatory T cells are distinguished by three key components: CD4, CD25, and the transcription factor FOXP3. Each plays a crucial role in Treg identity and function.

1. CD4: This surface glycoprotein categorizes Tregs as a subset of T helper cells. CD4 aids these cells in recognizing and responding to antigens. It acts as a co-receptor, enhancing the sensitivity of T cells to antigens presented by immune cells, thereby facilitating an immune response.
2. CD25: CD25 is the IL-2 receptor’s alpha chain, known to be highly expressed on Tregs. It allows Tregs to efficiently bind IL-2, a primary growth factor for T cells.
3. FOXP3: Expression of FOXP3 is vital for Treg differentiation and function; this transcription factor is considered the signature identifier for Tregs. Mutations in FOXP3 can disrupt Treg development, leading to immune dysregulation and autoimmune diseases. In humans, this can cause a disease called immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome — or IPEX for short. IPEX involves self-reactive lymphocytes that attack the host’s immune system.

Subtypes of Regulatory T cells

Tregs are categorized into two main subtypes: natural Tregs (nTregs) and peripherally induced Tregs (iTregs), each with distinct origins and functions

Natural Tregs (nTregs)

nTregs are a distinct lineage of T cells that originate in the thymus. These cells are necessary for recognizing and responding to the body’s own cells, thus maintaining self-tolerance and preventing autoimmunity. They are defined by their expression of the FOXP3 transcription factor, which is vital for their suppressive functions and development.

Induced Tregs (iTregs)

iTregs are generated from conventional naïve T cells in periphery tissues rather than the thymus. Their proliferation is influenced by environmental factors and the presence of cytokines like TGF-β. They play a significant role in regulating immune responses to external antigens, such as allergens and gut flora, helping the body maintain tolerance to these non-self elements. iTregs are particularly important in mucosal immunity, where they help in controlling immune responses to a vast array of environmental antigens.

Our current understanding of nTregs and iTregs — each with unique immunology origins and functions — underscores the complexity and adaptability of cell function in maintaining immune homeostasis.

Function and Role in Immune Response

Regulatory T cells are central to maintaining immune homeostasis and preventing autoimmune responses. They control the immune system primarily through suppression, targeting various immune cells. Tregs exert their influence in several ways:

• Direct cell-to-cell contact: Tregs can directly interact with other immune cells, including effector T cells and antigen-presenting cells, to modulate their activation. This interaction often leads to the suppression of these cells’ functions, preventing over-activation.
• Secretion of inhibitory cytokines: Tregs can secrete cytokines like IL-10 and TGF-β, which have broad anti-inflammatory effects. IL-10 inhibits the activation and function of many immune cells, including dendritic cells and macrophages. TGF-β helps maintain tissue homeostasis and has potent immunosuppressive properties.
• Metabolic disruption: Tregs can disrupt the metabolic function of effector T cells through a variety of mechanisms that are not yet well understood.
• Modulation of dendritic cell function: Tregs can alter the function of dendritic cells, which are crucial for initiating immune responses. By altering dendritic cell maturation and function, Tregs can prevent the activation of potentially autoreactive T cells.

Clinical Significance

The clinical significance of regulatory T cells extends beyond basic immunology, offering transformative potential in the treatment of various diseases through innovative immunotherapy approaches.

• Autoimmune diseases: Autoimmune disease can occur when the normal function of Tregs is impaired, allowing the immune system to attack the body’s own tissues. These diseases could potentially be managed by adjusting Treg activity. Boosting Treg function could suppress aberrant immune responses, providing a novel approach to treating diseases like rheumatoid arthritis, type 1 diabetes, and multiple sclerosis.
• Cancer immunotherapy: In cancer, Tregs often suppress the immune system’s ability to attack tumor cells. However, their role in cancer is complex. While Tregs can protect against inflammation-driven carcinogenesis, their immunosuppressive nature can also enable tumor growth by hindering the body’s ability to mount an effective anti-tumor response. The balance between Tregs’ protection and suppression of cancer cells is a key focus of current research.
• Transplantation: Tregs influence the success of transplantation medicine by promoting immune tolerance to transplanted organs and tissues. This is achieved through their suppressive action on immune responses that could lead to transplant rejection. Enhancing Treg function can potentially reduce patients’ dependence on long-term immunosuppressive medications, decreasing the risk of side effects and improving transplant outcomes.
• Allergies and inflammatory diseases: Modulating Treg activity could be beneficial in treating allergies and chronic inflammatory diseases by dampening inappropriate immune responses. This approach aims to suppress unnecessary inflammatory responses, providing relief in conditions like asthma, allergic rhinitis, and inflammatory bowel disease, where overactive immune responses exacerbate disease progression.

Tregs play a pivotal role in modulating our immune systems, so they can be of great benefit to researchers. Studying Treg cells allows scientists to target immunological processes that determine how we respond to harmful pathogens, diseases, and tumors.

Challenges in Cell Separation

To properly study regulatory T cells, they must be purified and isolated into a homogenous cell population. Although this can be done in a variety of ways, it is important to choose a cell separation method that works quickly and effectively, maintaining cell health and physiology.

Traditional methods like flow cytometry and magnetic-based cell isolation require expensive equipment that must be stored and properly maintained. These cell sorting cycles can also be time-consuming and require multiple attempts for large quantities. The harsh physical or magnetic forces involved in legacy cell isolation methods can damage the cell membranes, resulting in decreased proliferation or cell death. This often leads to complications in downstream applications.

Leveraging Innovative Microbubble Technology From Akadeum for Treg Separation

Because current isolation techniques can be time-consuming and induce stress on cells, the development of a gentle and effective method to obtain a high purity of a small target cell population for downstream analysis is of the utmost importance.

Akadeum’s microbubble technology represents a breakthrough in cell separation. The core of each microbubble is a hollow microsphere that lets researchers leverage the simplicity of floatation for quick and gentle removal of captured cells from a complex biological mixture. With buoyancy as the driving force powering microbubble-based separation, microbubbles provide consistent results and eliminate the need for extraneous equipment and consumables like magnets and columns.

Microbubble products enable reliable separation regardless of sample volume or container shape. Akadeum’s technology subverts traditional techniques that require various equipment and consumables to perform, fitting the process into a single container for self-separation that is exceptionally gentle on delicate cells.

Let’s Start a Conversation!

Understanding the intricacies of Treg function, from maintaining immune balance to their potential in treating various diseases, is vital to advancing research and cures for some of humanity’s most complex diseases. At Akadeum Life Sciences, we are committed to furthering scientific advancements to improve human health by overcoming existing limitations in separation technology.

If you face headaches in isolating rare cell types, talk with our scientific staff about your work, what troubles you’re facing, and how there could be a microbubble-based solution to overcome these obstacles.