Grakoui A, Donermeyer D L, Kanagawa O, Murphy K M, Allen P M
Center for Immunology and Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
J Immunol. 1999 Feb 15;162(4):1923-30.
We examined the role of the peptide/MHC ligand in CD4+ T cell differentiation into Th1 or Th2 cells using a TCR alphabeta transgenic mouse specific for hemoglobin (Hb)(64-76)/I-Ek. We identified two altered peptide ligands of Hb(64-76) that retain strong agonist activity but, at a given dose, induce cytokine patterns distinct from the Hb(64-76) peptide. The ability of these peptides to produce distinct cytokine patterns at identical doses is not due to an intrinsic qualitative property. Each peptide can induce Th2 cytokines at low concentrations and Th1 cytokines at high concentrations and has a unique range of concentrations at which these distinct effects occur. The pattern of cytokines produced from limiting dilution of naive T cells demonstrated that the potential to develop an individual Th1 or Th2 cell is stochastic, independent of Ag dose. We propose that the basis for the observed effects on the Th1/Th2 balance shown by the altered peptide ligands and the amount of Ag dose involves the modification of soluble factors in bulk cultures that are the driving force that polarize the population to either a Th1 or Th2 phenotype.
我们使用针对血红蛋白（Hb）（64 - 76）/I - Ek的TCRαβ转基因小鼠，研究了肽/MHC配体在CD4 + T细胞分化为Th1或Th2细胞过程中的作用。我们鉴定出两种Hb（64 - 76）的改变肽配体，它们保留了强大的激动剂活性，但在给定剂量下，诱导出与Hb（64 - 76）肽不同的细胞因子模式。这些肽在相同剂量下产生不同细胞因子模式的能力并非源于内在的定性特性。每种肽在低浓度时可诱导Th2细胞因子，在高浓度时可诱导Th1细胞因子，并且具有产生这些不同效应的独特浓度范围。从初始T细胞的有限稀释产生的细胞因子模式表明，单个Th1或Th2细胞发育的潜力是随机的，与抗原剂量无关。我们提出，改变肽配体和抗原剂量对Th1/Th2平衡产生观察到的影响的基础，涉及大量培养物中可溶性因子的修饰，这些因子是使群体极化到Th1或Th2表型的驱动力。
