Santana M A, Rosenstein Y
Facultad de Ciencias, Universidad Autónoma del Estado de Morelos, Chamilpa, Cuernavaca, México.
J Cell Physiol. 2003 Jun;195(3):392-401. doi: 10.1002/jcp.10258.
When activated, CD4(+) T cells differentiate into two major sub-populations differing in their profiles of secreted cytokines. Type One, or TH1, cells secrete IL-2, IFNgamma, and TNFbeta and mediate a cellular immune response. Type Two, or TH2, cells secrete IL-4, IL-5, IL-6, IL-10, and IL-13 and potentiate a humoral response. The nature of any specific immune response depends on the interaction of antigen-presenting cells and T cells. The role of antigen-presenting cells is to respond to the nature of the immune challenge and signal differentiation of CD4(+) T cells. A number of factors are involved in the effector phenotype of T cells-nature and affinity of antigen, co-receptors signals, and cytokine environment. T-cell differentiation is a complex process comprising four defined developmental stages: activation of particular cytokine genes, commitment of the cells, silencing of the opposing cytokine genes, and stabilization of the phenotype. In each of these stages, the cells respond to the products of many signaling cascades from many membrane-bound receptors. The stages in development are mediated by different molecular mechanisms, involving control of gene expression and chromatin remodeling. This review centers on the factors, cellular interactions, and molecular mechanisms involved in the maturation of naïve CD4(+) T lymphocytes into fully effector cells.
激活后,CD4(+) T细胞分化为两个主要亚群,它们分泌的细胞因子谱不同。第一类,即TH1细胞,分泌白细胞介素-2(IL-2)、干扰素γ(IFNγ)和肿瘤坏死因子β(TNFβ),介导细胞免疫反应。第二类,即TH2细胞,分泌白细胞介素-4(IL-4)、白细胞介素-5(IL-5)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)和白细胞介素-13(IL-13),增强体液反应。任何特定免疫反应的性质取决于抗原呈递细胞和T细胞的相互作用。抗原呈递细胞的作用是对免疫挑战的性质做出反应,并发出CD4(+) T细胞分化的信号。T细胞效应表型涉及多种因素——抗原的性质和亲和力、共受体信号以及细胞因子环境。T细胞分化是一个复杂的过程,包括四个明确的发育阶段:特定细胞因子基因的激活、细胞的定向分化、相对细胞因子基因的沉默以及表型的稳定。在这些阶段的每一个中,细胞都会对来自许多膜结合受体的许多信号级联反应的产物做出反应。发育阶段由不同的分子机制介导,涉及基因表达的控制和染色质重塑。本综述聚焦于参与幼稚CD4(+) T淋巴细胞成熟为完全效应细胞的因素、细胞间相互作用和分子机制。