How to Deplete CD4+ T Cells
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Technique Articles T cells GK1.5 CD4+

How to Deplete CD4+ T Cells in vivo

1. Introduction

T cells play a crucial role in advancing the broad field of immunological research, particularly CD4+ T cells. A practical method is T cell depletion in vivo, which has effectively stimulated numerous immune response and their applications in disease recovery [1, 2]. There are many ways to support this technique, but the anti-CD4 antibody clone GK1.5, is operative mainly because of its efficiency and specificity [3]. This review will discover the basic concept of in vivo T cell depletion, the benefits and limitations of GK1.5, other clones for several animal models, and current studies of GK1.5.   


2. Understanding CD4+ T Cell Depletion 

Targeting CD4+ T cells with the GK1.5 monoclonal antibodies is essential in understanding immune responses, functions, and disease progression. Besides, CD4+ T cell depletion in vivo offers significant insights into cancer immunotherapy, autoimmune diseases, and infectious diseases [4, 5]. 


Mechanism of action of GK1.5

Primarily, the mouse CD4 antigen binds with the monoclonal antibody GK1.5. Interacting with TCR (T cell receptor), this antigen with 55 kDa cell surface type I membrane glycoprotein functions as a co-receptor. It also cooperates with antigen-presenting cells’ class II MHC molecules. However, CD4 is essential for matured T cells to perform successfully and contributes to T cell advancement. This antibody’s interrelation with CD4 provides high efficiency and specificity for T cell depletion in vivo on the T cell surface without disturbing other immune functions [5, 6, 7]. Due to its specialization, researchers can precisely analyze how CD4+ T cells act in immunological responses and the pathophysiology of diseases. 

 

Drawbacks to consider

Despite its benefits, using GK1.5 requires caution. Off-target effects, where the antibody may bind to unintended cell types expressing CD4, can lead to nonspecific depletion or undesired immunological consequences [8]. Moreover, variations in experimental conditions, such as dosage and administration protocols, can affect the efficacy and specificity of GK1.5-mediated T-cell depletion. Thus, careful optimization and validation of experimental parameters are crucial.


Determining the Dose of GK1.5

The optimal dose of GK1.5 can vary depending on the specific experimental requirements and animal model used. Generally, doses ranging from 50 to 500 μg per injection have been reported in the literature for in vivo T cell depletion studies using GK1.5. Researchers should conduct dose-response experiments to determine the most effective dose for their particular setup, considering factors such as the animals' age, strain, and health status, as well as the duration and frequency of antibody administration.

 

3.  Alternative Clones for Different Animal Models

In addition to GK1.5, several alternative clones of anti-CD4 antibodies are available for different animal models:

 

Rat Models: Clone W3/25 is commonly used for T cell depletion in rats, offering comparable efficacy and specificity to GK1.5.

Non-Human Primate Models: Clone OKT4A is utilized for CD4+ T cell depletion in non-human primates with notable success.

Mouse Models: Clone YTS 191.1 is another alternative used in mice for depleting CD4+ T cells.

 

4.  Recent studies on CD4+ T Cell Depletion Utilizing GK1.5

Clausen et al. (2022) demonstrated that a murine model of autoimmune arthritis significantly decreases disease severity upon GK1.5-mediated CD4+ T cell depletion. It stimulates therapeutic potential by reducing cytokine production and attenuating joint injury [9]. 

Another study by Euler and Alter (2015) described a murine model of HIV infection in which therapy with GK1.5 antibodies meaningfully reduces viral load and the duration of disease development [10]. 

According to Phadke et al. (2023), combined treatments like GK1.5 AND CTLA-4 antibodies improve antitumor immunity in a mouse melanoma model by targeting CD4+ and regulatory T cells. Then, depleted regulatory T cells increase responses by effector T cells and enhance the regulation of tumors during cancer immunotherapy [11]. 

 

5. Conclusion

In vivo, T cell depletion using antibodies such as GK1.5 is a powerful approach to investigating the role of CD4+ T cells in health and disease. Understanding its advantages, pitfalls, dosage considerations, and recent research findings allows researchers to design experiments effectively and advance our knowledge of immune function and therapeutic interventions. Researchers can further optimize their studies by exploring alternative clones for different animal models and achieve reliable, reproducible results.

 

For information on how to deplete other immune cells in vivo please click here. 

 

To find our products: https://ichor.bio/anti-cd4-in-vivo-antibody-low-endotoxin-gk1-5-ich1042

 

6. References: 

1.  Kervevan J, Chakrabarti LA. Role of CD4+ T Cells in the Control of Viral Infections: Recent Advances and Open Questions. Int J Mol Sci. 2021 Jan 7;22(2):523. 

2. Chatzileontiadou DSM, Sloane H, Nguyen AT, Gras S, Grant EJ. The Many Faces of CD4+ T Cells: Immunological and Structural Characteristics. Int J Mol Sci. 2020 Dec 23;22(1):73. 

3.    Freise AC, Zettlitz KA, Salazar FB, Lu X, Tavaré R, Wu AM. ImmunoPET Imaging of Murine CD4+ T Cells Using Anti-CD4 Cys-Diabody: Effects of Protein Dose on T Cell Function and Imaging. Mol Imaging Biol. 2017 Aug;19(4):599-609. 

4.    Sun L, Su Y, Jiao A, Wang X, Zhang B. T cells in health and disease. Signal Transduct Target Ther. 2023 Jun 19;8(1):235. 

5.    Freise AC, Zettlitz KA, Salazar FB, Lu X, Tavaré R, Wu AM. ImmunoPET Imaging of Murine CD4+ T Cells Using Anti-CD4 Cys-Diabody: Effects of Protein Dose on T Cell Function and Imaging. Mol Imaging Biol. 2017 Aug;19(4):599-609.

6.    https://bioxcell.com/invivomab-anti-mouse-cd4-be0003-1 [Extracted information on June 29, 2024]

7.    https://www.thermofisher.com/antibody/product/CD4-Antibody-clone-GK1-5-Monoclonal/14-0041-82 [Extracted information on June 29, 2024]. 

8.   Mandel TE, Dillon H, Koulmanda M. The effect of a depleting anti-CD4 monoclonal antibody on T cells and fetal pig islet xenograft survival in various strains of mice. Transpl Immunol. 1995 Sep;3(3):265-72. 

9.  Clausen AS, Christensen C, Christensen E, Cold S, Kristensen LK, Hansen AE, Kjaer A. Development of a 64Cu-labeled CD4+ T cell targeting PET tracer: evaluation of CD4 specificity and its potential use in collagen-induced arthritis. EJNMMI Res. 2022 Sep 16;12(1):62. 

10.  Euler Z, Alter G. Exploring the potential of monoclonal antibody therapeutics for HIV-1 eradication. AIDS Res Hum Retroviruses. 2015 Jan;31(1):13-24. 

11.  Phadke MS, Li J, Chen Z, Rodriguez PC, Mandula JK, Karapetyan L, Forsyth PA, Chen YA, Smalley KSM. Differential requirements for CD4+ T cells in the efficacy of the anti-PD-1+LAG-3 and anti-PD-1+CTLA-4 combinations in melanoma flank and brain metastasis models. J Immunother Cancer. 2023 Dec 6;11(12): e007239.