Buckner Jane H, Nepom Gerald T
Benaroya Research Institute at Virginia Mason, The University of Washington School of Medicine, Seattle, WA, USA.
Benaroya Research Institute at Virginia Mason, The University of Washington School of Medicine, Seattle, WA, USA.
J Autoimmun. 2016 Jul;71:44-50. doi: 10.1016/j.jaut.2016.02.009. Epub 2016 Mar 3.
Autoreactive lymphocytes display a programmed set of characteristic effector functions and phenotypic markers that, in combination with antigen-specific profiling, provide a detailed picture of the adaptive immune response in Type 1 diabetes (T1D). The CD4+ T cell effector compartment (referred to as "Teff" in this article) has been extensively analyzed, particularly because the HLA genes most strongly associated with T1D are MHC class II alleles that form restriction elements for CD4+ T cell recognition. This "guilt by association" can now be revisited in terms of specific immune mechanisms and specific forms of T cell recognition that are displayed by Teff found in subjects with T1D. In this review, we describe properties of Teff that correlate with T1D, and discuss several characteristics that advance our understanding of disease persistence and progression. Focusing on functional disease-associated immunological pathways within these Teff suggests a rationale for next-generation clinical trials with targeted interventions. Indeed, immune modulation therapies in T1D that do not address these properties of Teff are unlikely to achieve durable clinical response.
自身反应性淋巴细胞表现出一系列程序化的特征性效应功能和表型标志物，这些与抗原特异性分析相结合，为1型糖尿病（T1D）的适应性免疫反应提供了详细图景。CD4+ T细胞效应亚群（本文中称为“Teff”）已得到广泛分析，特别是因为与T1D关联最紧密的HLA基因是MHC II类等位基因，它们构成了CD4+ T细胞识别的限制元件。现在可以从T1D患者中发现的Teff所展示的特定免疫机制和特定形式的T细胞识别角度重新审视这种“关联有罪”。在本综述中，我们描述了与T1D相关的Teff特性，并讨论了几个有助于我们理解疾病持续存在和进展的特征。关注这些Teff内与疾病相关的功能性免疫途径为下一代靶向干预临床试验提供了理论依据。事实上，T1D中未针对Teff这些特性的免疫调节疗法不太可能实现持久的临床反应。
