The article reviews the differentiation and functions of CD4+ T cells, which are crucial for a regulated immune response to pathogens. Naive CD4+ T cells differentiate into various effector subtypes, including Th1, Th2, Th17, regulatory T cells (Tregs), follicular helper T cells (Tfh), and Th9, each with distinct cytokine profiles. The differentiation process is influenced by cytokine signaling pathways, lineage-specific transcription factors, and epigenetic modifications. Th1 cells secrete IFN-γ, lymphotoxin α (LTA), and IL-2, playing roles in eliminating intracellular pathogens and organ-specific autoimmunity. Th2 cells produce IL-4, IL-5, IL-9, IL-13, IL-10, IL-25, and amphiregulin, contributing to allergic responses and asthma. Th17 cells secrete IL-17A, IL-17F, IL-21, and IL-22, involved in immune responses against extracellular bacteria and fungi, and autoimmune diseases. Tregs, including natural and induced Tregs, produce IL-10, TGF-β, and IL-35, maintaining immunologic tolerance. Tfh cells, expressing CXCR5, secrete IL-21 and IL-4, promoting humoral immunity and B-cell differentiation. The article also discusses the plasticity of CD4+ T cell subsets, particularly Tregs and Th17 cells, and their potential risks in autoimmune diseases and organ transplant.The article reviews the differentiation and functions of CD4+ T cells, which are crucial for a regulated immune response to pathogens. Naive CD4+ T cells differentiate into various effector subtypes, including Th1, Th2, Th17, regulatory T cells (Tregs), follicular helper T cells (Tfh), and Th9, each with distinct cytokine profiles. The differentiation process is influenced by cytokine signaling pathways, lineage-specific transcription factors, and epigenetic modifications. Th1 cells secrete IFN-γ, lymphotoxin α (LTA), and IL-2, playing roles in eliminating intracellular pathogens and organ-specific autoimmunity. Th2 cells produce IL-4, IL-5, IL-9, IL-13, IL-10, IL-25, and amphiregulin, contributing to allergic responses and asthma. Th17 cells secrete IL-17A, IL-17F, IL-21, and IL-22, involved in immune responses against extracellular bacteria and fungi, and autoimmune diseases. Tregs, including natural and induced Tregs, produce IL-10, TGF-β, and IL-35, maintaining immunologic tolerance. Tfh cells, expressing CXCR5, secrete IL-21 and IL-4, promoting humoral immunity and B-cell differentiation. The article also discusses the plasticity of CD4+ T cell subsets, particularly Tregs and Th17 cells, and their potential risks in autoimmune diseases and organ transplant.