肿瘤细胞治疗研究
英文原题：Engineered antigen-specific T regulatory cells suppress autoreactivity to the anti-glomerular basement membrane disease antigen.
Engineered antigen-specific T regulatory cells suppress autoreactivity to the anti-glomerular basement membrane disease antigen.
抗肾小球基底膜（anti-GBM）病伴有抗原特异性调节性T细胞（Tregs）不足和抗原特异性常规T细胞克隆扩增。
抗肾小球基底膜（anti-GBM）病伴随抗原特异性调节性T细胞（Tregs）不足和抗原特异性常规T细胞的克隆扩增。尤其适用于由人类白细胞抗原-DRB1∗1501呈递的IV型胶原免疫优势T细胞自身表位α3(IV)NC1 135-145。在此，我们研究了表达针对α3(IV)NC1 135-145的GBM-T细胞受体（TCR）的工程化Tregs是否能更好地抑制自身免疫。GBM-TCR Treg细胞产品表现出表型稳定的Treg表型，产生α3(IV)NC1 135-145特异性功能反应，并且与多克隆Tregs或无关TCR转导的Tregs相比，是自身反应性常规T细胞和旁观者常规T细胞的更优抑制者。我们还发现GBM-TCR Tregs将其他免疫细胞如树突状细胞和B细胞调节为更耐受的表型。重要的是，我们的发现支持将GBM-TCR Tregs开发为抗GBM病的一种有前景的细胞疗法。
Anti-glomerular basement membrane (anti-GBM) disease is accompanied by insufficient antigen-specific regulatory T cells (Tregs) and clonally expanded antigen-specific conventional T cells. In particular, this applied to the immunodominant T cell autoepitope of type IV collagen, α3(IV)NC1 135-145 , presented by human leukocyte antigen-DRB1∗1501. Here, we investigated whether Tregs engineered to express GBM-T cell receptors (TCR) specific for α3(IV)NC1 135-145 better suppress autoimmunity. The GBM-TCR Treg cell product exhibited a phenotypically stable Treg phenotype, produced α3(IV)NC1 135-145 -specific functional responses, and were superior suppressors of autoreactive conventional T cells and bystander conventional T cells compared to polyclonal Tregs or irrelevant TCR-transduced Tregs. We also found that GBM-TCR Tregs modulate other immune cells like dendritic cells and B cells to a more tolerogenic phenotype. Importantly, our findings support the development of GBM-TCR Tregs as a promising cell-based therapy for anti-GBM disease.
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