Soluble CD4 (sCD4)

Specification

• Cat#: THP-0227
• Product Name: Soluble CD4 (sCD4)
• Description: CD4 is a transmembrane glycoprotein that is expressed predominantly on thymocytes and a subset of mature T lymphocytes. It is a standard phenotype marker for the identification of T cell populations.
• Species: Human
• Molecular Weight: 40 kDa
• Source: Baculovirus infected Sf21 cells
• Introduction: CD4 is expressed along with CD8 on double positive T cells during their development in the thymus. Either CD4 or CD8 expression is then lost, giving rise to single positive (SP) CD4+ or CD8+ mature T cells. CD4+ SP cells, also known as T helper cells, further differentiate into multiple subsets of CD4+ cells including Th1, Th2, Th9, Th17,Th22, Tfh, and Treg cells which regulate humoral and cellular immunity. In human, CD4 is additionally expressed on macrophages, neutrophils, monocytes, NK cells, and neurons and glial cells in the brain. CD4 binds directly to MHC class II molecules on antigen presenting cells. This interaction contributes to the formation of the immunological synapse which is focused around the TCR-MHC class II-antigenic peptide interaction. CD4 also functions as a chemotactic receptor for IL-16 and, in human, as a coreceptor for the gp120 surface glycoprotein of HIV-1.
• Purity: >90%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining.
• Formulation: Lyophilized from a 0.2 μm filtered solution in PBS with BSA as a carrier protein.
• Biological Activity: Measured by the ability of the immobilized protein to support the adhesion of HeLa human cervical epithelial carcinoma cells. When 5 x 10＾4 cells/well are added to human recombinant CD4 coated plates (2.5 μg/mL, 100 μL/well), approximately 50-80% of the cells will adhere after 1 hour at 37 centigrade.
• Reconstitution: Reconstitute at 50 μg/mL in sterile PBS containing at least 0.1% human or bovine serum albumin.

Pharmaceutical Information

• Applications: CD4 binds directly to MHC class II molecules on antigen presenting cells. This interaction contributes to the formation of the immunological synapse which is focused around the TCR-MHC class II-antigenic peptide interaction. CD4 also functions as a chemotactic receptor for IL-16 and, in human, as a coreceptor for the gp120 surface glycoprotein of HIV-1.
• Examples of Clinical Use: Formation of the immunological synapse which is focused around the TCR-MHC class II-antigenic peptide interaction.
• Affected organisms: Humans

Related Reading

Introduction

Soluble CD4 (sCD4) is a truncated form of the CD4 cell surface glycoprotein, which is primarily known for its crucial role in facilitating the immune response through T cell activation. In its soluble form, sCD4 is released into the bloodstream and other bodily fluids through various mechanisms, where it has been implicated in multiple physiological and pathological processes. This literature review aims to provide a comprehensive analysis of the current state of knowledge surrounding sCD4, including its biological functions, diagnostic utility, and potential as a therapeutic target.

Biological Functions of Soluble CD4

Soluble CD4 arises from the proteolytic cleavage of the extracellular domain of membrane-bound CD4 by disintegrin and metalloproteinase domain-containing enzymes (ADAMs) and other proteases. As a result of this cleavage, sCD4 is released into circulation, where it exerts a range of immunomodulatory functions.

One of the primary roles of sCD4 is its ability to compete with membrane-bound CD4 for binding to the human immunodeficiency virus (HIV) envelope glycoprotein gp120. By binding to gp120, sCD4 prevents viral entry into target CD4+ T cells, making it a potential therapeutic agent against HIV infection ⁽¹⁾.

Furthermore, sCD4 has been shown to modulate immune responses by influencing T cell activation and cytokine production. It can enhance or inhibit T cell activation depending on the context and concentration, playing a role in immune homeostasis ⁽²⁾. Additionally, sCD4 can affect the function of antigen-presenting cells and B cells, contributing to a broader impact on the adaptive immune response.

Diagnostic Utility of sCD4

Given its involvement in immune regulation and interactions with HIV gp120, sCD4 has been explored as a potential diagnostic biomarker for various medical conditions.

In the context of HIV infection, the level of sCD4 in the plasma has been investigated as a surrogate marker for CD4+ T cell counts, which are indicative of the progression of HIV disease. Studies have shown a correlation between decreased sCD4 levels and declining CD4+ T cell counts, making sCD4 a potential candidate for monitoring disease progression and treatment efficacy in HIV patients ⁽³⁾.

In addition to HIV, sCD4 has been studied as a diagnostic marker in autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Elevated levels of sCD4 have been reported in the serum of patients with active SLE, suggesting its potential as a disease activity biomarker ⁽⁴⁾. Similarly, sCD4 levels have been found to be elevated in RA patients, correlating with disease severity and inflammation ⁽⁵⁾.

Therapeutic Implications of sCD4

The immunomodulatory properties of sCD4 have led to its consideration as a potential therapeutic target for several diseases.

As mentioned earlier, sCD4's ability to bind to HIV gp120 and inhibit viral entry into CD4+ T cells has prompted investigations into its use as an anti-HIV therapeutic agent. However, challenges such as low bioavailability and rapid clearance from the circulation have hindered its clinical application. Researchers continue to explore novel approaches to enhance the stability and effectiveness of sCD4-based therapies for HIV ⁽⁶⁾.

Moreover, sCD4 has shown promise in ameliorating autoimmune diseases by dampening immune responses. In preclinical models of SLE and RA, sCD4 administration has been associated with reduced disease severity and inflammation ⁽⁷⁾. However, more research is needed to understand the potential side effects and optimize the therapeutic dosing of sCD4 in these contexts.

Conclusion

Soluble CD4 (sCD4) represents a multifunctional protein with significant implications in immune regulation, disease diagnostics, and therapeutic development. As a truncated form of the CD4 cell surface glycoprotein, sCD4 participates in immune responses through its interactions with HIV gp120 and T cell activation. Its diagnostic utility has been explored in HIV infection, as well as autoimmune diseases like SLE and RA, where it holds promise as a biomarker for disease monitoring and severity assessment. Additionally, sCD4 shows potential as a therapeutic agent for HIV and autoimmune diseases, but challenges related to its bioavailability and stability need to be addressed for successful clinical application. As research in this field continues to evolve, a deeper understanding of sCD4's roles and mechanisms will open up new avenues for utilizing this soluble protein in the diagnosis and treatment of various immunological and infectious diseases.

References

1. Eckert, D. M., & Kim, P. S. (2001). Mechanisms of viral membrane fusion and its inhibition. Annual Review of Biochemistry, 70, 777-810.
2. Smith-Garvin, J. E., Koretzky, G. A., & Jordan, M. S. (2009). T cell activation. Annual Review of Immunology, 27, 591-619.
3. Malaspina, A., Moir, S., Ho, J., Wang, W., Howell, M. L., O'Shea, M. A., ... & Fauci, A. S. (2006). Appearance of immature/transitional B cells in HIV-infected individuals with advanced disease: Correlation with increased IL-7. Proceedings of the National Academy of Sciences, 103(7), 2262-2267.
4. Bonakdar, Z. S., Rezaieyazdi, Z., Sahebari, M., Rasouli, M., & Shirzad, H. (2016). The potential use of soluble CD4 as a biomarker of systemic lupus erythematosus disease activity. Lupus, 25(2), 144-149.
5. Valbracht, J., Egerer, K., & Feist, E. (2007). Soluble CD4 levels in rheumatoid arthritis: Relation to disease activity, radiological damage, and circulating markers of inflammation. The Journal of Rheumatology, 34(9), 1879-1884.
6. Chauhan, A., Tikoo, A., Kapur, A., & Singh, M. (2019). CD4-based immunotherapeutic strategies for HIV infection: Advances, challenges, and future directions. Medical Research Reviews, 39(1), 325-367.
7. Prabhavathy, D., Ling, E. A., Singh, M., & Lu, J. (2004). Soluble CD4 as a therapeutic agent for human immunodeficiency virus. Journal of Molecular Medicine, 82(12), 815-825.