CD25 Marker
CD25, a key molecule in immune regulation, is integral to the function of activated lymphocytes and regulatory T cells. It's central in mediating immune responses, with implications in autoimmune diseases and cancer.
Key Takeaways:
- CD25, part of the IL-2 receptor, is crucial in immune response regulation.
- Found on T cells, NK cells, Tregs, and others; upregulated during immune activation.
- Vital for cellular immune responses and maintaining immune homeostasis.
- Serves as a biomarker in autoimmune diseases, allergies, and certain cancers.
- Targeted in immunotherapy for diseases like multiple sclerosis and various cancers.
What is CD25?
CD25, also known as Cluster of Differentiation 25, is an essential molecule involved in immune responses. It is the alpha chain of the high-affinity interleukin-2 receptor (IL2RA) and is also referred to as T11 antigen. This 65kDa transmembrane glycoprotein is primarily located on the cell surface of activated lymphocytes, playing a crucial role in their functioning. CD25 belongs to a gene family consisting of other members such as CD5, CD10, and CD19, which share similarities in both structure and function.
What is CD25?
CD25, also known as Cluster of Differentiation 25, is an essential molecule involved in immune responses. It is the alpha chain of the high-affinity interleukin-2 receptor (IL2RA) and is also referred to as T11 antigen. This 65kDa transmembrane glycoprotein is primarily located on the cell surface of activated lymphocytes, playing a crucial role in their functioning. CD25 belongs to a gene family consisting of other members such as CD5, CD10, and CD19, which share similarities in both structure and function.
Where is CD25 expressed?
Scientists originally believed CD25 was expressed on natural killer cells but it has since been shown to also be expressed on activated T lymphocytes. In contrast to CD4 or CD8 antigens that are restricted to either alpha/beta or gamma/delta T-cell receptors respectively, CD25 appears on both types of receptor bearing cells. CD25 is also expressed on mature natural killer (NK) cells, recent thymic emigrants (RTE), eosinophils, basophils and some CD34+ hematopoietic progenitors.
CD25 expression has also been observed in regulatory T cells (Tregs), which are a specialized subset of T lymphocytes with immunosuppressive properties. Tregs play a crucial role in maintaining immune homeostasis and preventing excessive immune responses. CD25 serves as a key marker for identifying and characterizing Tregs, as it is highly expressed on their cell surface.
Furthermore, CD25 expression can be dynamically regulated in response to various stimuli. For instance, during immune activation or inflammation, the expression of CD25 on T cells can be upregulated, indicating their increased responsiveness to immune signals. This upregulation allows for the expansion of antigen-specific T cells and the generation of an effective immune response.
What does CD25 bind to?
CD25 binds with the high-affinity IL-2 which transmits an intracellular signalling cascade that upregulates expression of Bcl-2 family members which eventually suppresses apoptosis of CD4 T-cells. CD25 thereby acts as a high-affinity IL-2 receptor, allowing for mediation of T-cell proliferation.
What is the role of CD25?
Unlike CD25+ B-cells that function in the adaptive immune response against an antigen, CD25+ T-cells are involved in cellular immune responses. Studies of mice deficient in either IL-2 or its receptor show evidence for defective T-cell immunity, suggesting the role of CD25 is to mediate cellular immune response. Loss of CD25 expression correlates with increased IL-2 production, improved Cytotoxic T-cells (CTL) function and Th1 differentiation, whereas concomitant upregulation serves to limit immune responsiveness towards self antigens.
Mechanism of CD25 upregulation in T cells
CD25 expression in T cells is upregulated through various pathways. Upon mitogen or allo-antigen binding to T cells, activation of their T cell receptors triggers a calcium influx, leading to the phosphorylation of protein kinase C. This cascade ultimately results in the upregulation of CD25, with levels reaching 5- to 20-fold greater than the entire heterotrimeric IL2R complex. Furthermore, CD25 expression is stimulated by contact with IL2, creating a positive feedback loop involving the binding of signal transducer and activator of transcription 5 (STAT5) to the IL2RA (CD25) gene locus. Studies have demonstrated that peak CD25 expression occurs within 48-96 hours after activation, with up to 60,000 molecules per T cell surface. However, CD25 expression gradually declines, with an 80% decrease observed by 10-21 days. In addition to its impact on IL2RA expression, IL2 binding to its heterotrimeric receptor stimulates T cell growth and effector function. This process involves signal transduction pathways, leading to the phosphorylation and translocation of dimerized STAT5 proteins, activated mitogen-activated protein kinase (MAPK), or p70 S6 kinase (p70S6K) to the nucleus. These events further promote transcription and contribute to T cell activation.
Can CD25 serve as a biomarker?
CD25 has been recognized as a valuable biomarker in various clinical settings. The expression of CD25 on T-cells can indicate immune activation and has been associated with several conditions, including autoimmune diseases, allergic reactions, and certain types of cancers. For example, the alterations in the ratio of CD4+CD25+ regulatory T-cells (Tregs) in the peripheral blood of individuals with sepsis have been linked to clinical outcomes, including survival or mortality. These findings suggest that CD4+CD25+ Tregs could potentially serve as a biomarker for accurately evaluating the prognosis of patients with sepsis. Monitoring CD25 expression can help assess disease activity, predict treatment response, and guide therapeutic decisions. Additionally, CD25 expression on regulatory T-cells (Tregs) has been linked to immune suppression and tolerance, making it relevant in studies focused on immune modulation and immunotherapy. Therefore, CD25 serves as a promising biomarker with diagnostic, prognostic, and therapeutic implications in various clinical contexts.
Diseases associated with elevated CD25 levels
Autoimmune Disease | Neoplasia | Infection | Other |
Asthma | Leukaemias | Human immunodeficiency virus | Haemophagocytic lymphocytichistiocytosis |
Aplastic anaemia | Lymphomas | Epstein-Barr Virus | General anaesthesia |
Idiopathic thrombocytopenia | Solid tumors e.g. sarcomas, head and neck cancer, lung adenocarcinoma | Pulmonary tuberculosis | End stage renal disease |
Uveitis | Multiple myeloma | Sepsis | Burns |
Multiple Sclerosis | Allograft rejection |
Role of CD25 in cancer
CD25 expression is prominently observed in various hematological malignancies, whereas its presence is limited to specific types of solid tumors. In both hematological and solid malignancies, soluble CD25 (sCD25) serves as a surrogate marker for CD25 expression and has been found to be significantly increased in the serum of affected patients. Elevated sCD25 levels have been associated with certain solid tumors such as lung adenocarcinoma, esophageal cancer, and head and neck cancer. Likewise, hematological malignancies including specific acute leukemias and non-Hodgkin's lymphoma (NHL) exhibit high levels of sCD25. These findings highlight the potential of sCD25 as a diagnostic and prognostic marker in different cancer types, enabling better understanding and management of these diseases. Understanding the intricate interplay between CD25 expression, tumor biology, and treatment response holds promise for personalized cancer therapies.
Therapeutic potential of CD25
Researchers have used CD25 as an immunotherapy target for treating multiple sclerosis with T-regulatory cells. CD25 has also been identified as a potential target for the treatment of Hashimoto's thyroiditis, but this is still currently experimental. Siltuximab is a monoclonal antibody which seeks to inhibit CD25 activation for treatment of immune disorders.
The use of anti-CD25 antibodies presents the risk of inducing apoptosis in T suppressor cell populations, thus reducing Treg function and causing autoimmune pathology. Monoclonal antibodies targeting CD25, such as daclizumab and basiliximab, have been explored in clinical trials for different cancer types. These antibodies aim to block IL-2 signaling and disrupt the function of regulatory T-cells (Tregs), which can suppress antitumor immune responses. By targeting CD25, immunotherapy strategies seek to enhance the immune system's ability to recognize and attack cancer cells.. This selective effect ensures minimal impact on healthy immune function.
In mice, anti-CD25 antibody is an effective method of depleting CD25(+) FOXP3(+) T regulatory cells (Tregs) in vivo and enhancing cancer immunity.
The Role of CD25 and PD-1 in Immune System Regulation
CD25 and PD-1 are two proteins that, when found on regulatory T cells (Tregs) and activated T cells respectively, help to keep the immune system balanced by controlling its response. Without these important players in regulation of immunity, autoimmune diseases may arise as a result of an unbridled immune response.
Research indicates that PD-1 signaling can inhibit the function of CD25+ Tregs, leading to an unrestrained immune response. Cancer cells are experts at using this mechanism to elude detection from the immune system by repressing CD25+ Tregs through PD-1 signaling.
Conversely, targeting PD-1 might boost the capacity of CD25+ Tregs, leading to a better-regulated immune reaction and potentially improving outcomes in autoimmune diseases or transplant rejection.
Written by Pragna Krishnapur
Pragna Krishnapur completed her bachelor degree in Biotechnology Engineering in Visvesvaraya Technological University before completing her masters in Biotechnology at University College Dublin.
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