Cd4, a well-known gene, codes for the CD4 protein which is predominantly expressed on the surface of T helper cells. CD4+ T cells play a crucial role in the immune response, serving as key regulators that help other immune cells, such as B cells and cytotoxic T cells, to function effectively. They are involved in various immune-related pathways, for example, cytokine-mediated signaling pathways that influence T cell differentiation. Their biological importance lies in their ability to mount appropriate immune responses against pathogens, control viral replication, and contribute to anti-tumor immunity [1,2,3,4].

CD4+ T cells can differentiate into various subsets, each with distinct functions. The discovery of subset-defining master transcription factors and the Th1/Th2 paradigm has significantly advanced our understanding of CD4+ T cell differentiation [1]. Moreover, the appearance of cytotoxic CD4+ T cells (CD4 CTLs) during viral infections and in cancer has been observed. These CD4 CTLs can directly kill infected or transformed cells, compensating for exhausted CD8+ CTL responses in chronic viral infections and acting as anti-tumor effectors in solid cancers [2,3,4]. Transcriptional and epigenetic networks control CD4 CTL differentiation, and histone deacetylases may play a role in their generation [2].

In conclusion, Cd4 is essential for the proper functioning of the immune system, with CD4+ T cells having diverse functions in immunity and disease. Studies on CD4+ T cells, including those potentially using gene knockout (KO) or conditional knockout (CKO) mouse models (although not directly described in the given references but inferred from the general field knowledge), contribute to our understanding of their roles in chronic viral infections and cancer, potentially paving the way for new therapeutic strategies targeting these diseases [1,2,3,4].

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. Preglej, Teresa, Ellmeier, Wilfried. 2022. CD4+ Cytotoxic T cells - Phenotype, Function and Transcriptional Networks Controlling Their Differentiation Pathways. In Immunology letters, 247, 27-42. doi:10.1016/j.imlet.2022.05.001. https://pubmed.ncbi.nlm.nih.gov/35568324/

3. Malyshkina, Anna, Brüggemann, Alicia, Paschen, Annette, Dittmer, Ulf. 2023. Cytotoxic CD4+ T cells in chronic viral infections and cancer. In Frontiers in immunology, 14, 1271236. doi:10.3389/fimmu.2023.1271236. https://pubmed.ncbi.nlm.nih.gov/37965314/

4. Wang, Boyu, Hu, Shaojie, Fu, Xiangning, Li, Lequn. 2022. CD4+ Cytotoxic T Lymphocytes in Cancer Immunity and Immunotherapy. In Advanced biology, 7, e2200169. doi:10.1002/adbi.202200169. https://pubmed.ncbi.nlm.nih.gov/36193961/