CD4 is a transmembrane glycoprotein serving as a primary receptor for HIV-1 infection 12 and human herpesvirus 7 3. Beyond pathogen recognition, CD4 functions as a coreceptor for MHC class II-restricted T cell activation and is expressed on diverse T cell populations with distinct immunological roles. CD4+ T cells encompass multiple functional subsets. Regulatory T cells (Tregs), identified as CD4+FOXP3+ cells, comprise approximately 20% of CD4+ T cells in skin and preferentially localize to perivascular and perifollicular regions 4. Alternative regulatory populations include CD4+CD25-LAG-3+ T cells that produce high IL-10 levels and exhibit immunosuppressive activity 5. CD4+ T cells also demonstrate considerable plasticity; IL-4 can convert human CD4+ thymocytes to CD8+ T cells through de novo CD8αβ synthesis 6. Additionally, cytotoxic CD4+ T cells (CD4 CTLs) directly eliminate HLA-II-expressing senescent fibroblasts through MHC class II-dependent recognition 7. Clinically, CD4 dysfunction underlies Immunodeficiency 79, while HIV-1 Vpu-mediated CD4 downregulation facilitates viral evasion 8. The CD4 molecule's role in both immune regulation and therapeutic targeting, including nanobody-modified AAV vectors for CD4+ T cell gene therapy 9, underscores its clinical significance in infectious disease and immunotherapy development.