Cd4, also known as cluster of differentiation 4, is a glycoprotein expressed on the surface of immune cells, most notably a subset of T lymphocytes (CD4+ T cells). CD4+ T cells play a crucial role in the immune response by providing help to other immune cells, such as B cells and cytotoxic T cells. They are involved in various pathways related to immune cell differentiation and function, including cytokine-mediated signaling, T-cell receptor signaling, and the regulation of immune cell fate decisions. Their proper function is essential for a robust and balanced immune system, protecting the body against pathogens and potentially cancer cells [1-3].

CD4+ T cells can differentiate into multiple subsets, each with distinct functions. For example, the discovery of master transcription factors led to the Th1/Th2 paradigm, but in-vivo studies have shown more complex lineage-defining transcriptional networks [1]. CD4+ T cells can also exhibit cytotoxic activity (CD4+ CTLs), especially during viral infections, where they may compensate for exhausted CD8+ CTL responses and control viral replication [2, 4-6]. Their differentiation can be influenced by factors like cytokine production from antigen-presenting cells and innate cells, and signals downstream of the T-cell receptor, which determine whether they become T follicular helper cells or T effector cells [1]. Additionally, glutaminolysis has been found to play a role in the differentiation of CD4+ T cells, and abnormal differentiation of peripheral CD4+ T cells is associated with diseases like autoimmune diseases, transplantation rejection, and irritability [2]. Aging can also lead to changes in the CD4+ T-cell pool, making it involved in immunosenescence [3].

In conclusion, Cd4 is essential for the proper functioning of CD4+ T cells, which are central to the immune response. Through model-based research, we have learned that Cd4-related processes in CD4+ T cells are involved in various disease conditions, including viral infections, cancer, autoimmune diseases, and aging-related immunosenescence. Understanding Cd4 and its associated mechanisms provides insights into immune-mediated diseases and may offer potential therapeutic targets [1-3].

References:

1. Ruterbusch, Mikel, Pruner, Kurt B, Shehata, Laila, Pepper, Marion. . In Vivo CD4+ T Cell Differentiation and Function: Revisiting the Th1/Th2 Paradigm. In Annual review of immunology, 38, 705-725. doi:10.1146/annurev-immunol-103019-085803. https://pubmed.ncbi.nlm.nih.gov/32340571/

2. Liu, Tong, Ren, Shaohua, Sun, Chenglu, Zhao, Pengyu, Wang, Hao. 2023. Glutaminolysis and peripheral CD4+ T cell differentiation: from mechanism to intervention strategy. In Frontiers in immunology, 14, 1221530. doi:10.3389/fimmu.2023.1221530. https://pubmed.ncbi.nlm.nih.gov/37545506/

3. Xia, Tingting, Zhou, Ying, An, Jiayao, Zhao, Xin, Gao, Xiumei. 2024. Benefit delayed immunosenescence by regulating CD4+T cells: A promising therapeutic target for aging-related diseases. In Aging cell, 23, e14317. doi:10.1111/acel.14317. https://pubmed.ncbi.nlm.nih.gov/39155409/