Inducing antigen-specific tolerance during an established immune response typically requires non-specific immunosuppressive signalling molecules. Hence, standard treatments for autoimmunity trigger global immunosuppression. Here we show that established antigen-specific responses in effector T cells and memory T cells can be suppressed by a polymer glycosylated with N-acetylgalactosamine (pGal) and conjugated to the antigen via a self-immolative linker that allows for the dissociation of the antigen on endocytosis and its presentation in the immunoregulatory environment. We show that pGal–antigen therapy induces antigen-specific tolerance in a mouse model of experimental autoimmune encephalomyelitis (with programmed cell-death-1 and the co-inhibitory ligand CD276 driving the tolerogenic responses), as well as the suppression of antigen-specific responses to vaccination against a DNA-based simian immunodeficiency virus in non-human primates. Our findings show that pGal–antigen therapy invokes mechanisms of immune tolerance to resolve antigen-specific inflammatory T-cell responses and suggest that the therapy may be applicable across autoimmune diseases.

在已建立的免疫应答过程中诱导抗原特异性耐受通常需要非特异性免疫抑制信号分子。因此，自身免疫的标准治疗会引发全身免疫抑制。在这里，我们表明效应 T 细胞和记忆 T 细胞中已建立的抗原特异性反应可以被 N-乙酰半乳糖胺 (pGal) 糖基化的聚合物抑制，并通过自毁连接体与抗原缀合，从而使抗原解离内吞作用及其在免疫调节环境中的表现。我们表明，pGal 抗原疗法在实验性自身免疫性脑脊髓炎小鼠模型中诱导抗原特异性耐受（程序性细胞死亡 1 和共抑制配体 CD276 驱动耐受性反应），并抑制抗原特异性耐受。非人灵长类动物对基于 DNA 的猿猴免疫缺陷病毒疫苗接种的反应。我们的研究结果表明，pGal 抗原疗法会调用免疫耐受机制来解决抗原特异性炎症 T 细胞反应，并表明该疗法可能适用于自身免疫性疾病。