改造人体防御系统中的调节性细胞有可能让科学家使用有针对性的方式抑制一种过度活跃的自体免疫应答并减少对抑制整个免疫系统的药物的需求。
Hans Stauss及其同事调查了设计有能力减少炎症而不论最初引发因素是什么的调节性T细胞的两种策略。在一组实验室实验中，这组科学家使用基因转移从而制造出了具有特异性的调节性T细胞。对于第二组，这组科学家转换了正常T细胞的特异性并让它们具有了调节功能。这组科学家然后利用一种小鼠关节炎模型研究了这种改造后的调节性T细胞的免疫抑制效果，在实验中，科学家把这些细胞静脉注射到了这些小鼠体内。这种改造后的调节性T细胞在关节炎的位置积聚。在那里，这些细胞抑制了炎症和骨损坏。这组作者说，这种改造过程的速度以及这种细胞减少身体炎症反应的能力让这种方法有潜力用于一大批目前依赖于全身免疫抑制疗法的自体免疫疾病。（生物谷Bioon.com）
生物谷推荐原始出处：
PNAS November 2, 2009, doi: 10.1073/pnas.0907396106
Adoptive therapy with redirected primary regulatory T cells results in antigen-specific suppression of arthritis
Graham P. Wrighta,1, Clare A. Notleyb, Shao-An Xuea, Gavin M. Bendlec, Angelika Hollera, Ton N. Schumacherc, Michael R. Ehrensteinb and Hans J. Staussa,1
aDepartment of Immunology, University College London, Royal Free Hospital, London NW3 2PF, United Kingdom;
bDepartment of Medicine, Centre for Rheumatology, University College London, London W1T 4JF, United Kingdom; and
cNetherlands Cancer Institute, Department of Immunology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Regulatory T cells (Tregs) can suppress a wide range of immune cells, making them an ideal candidate for the treatment of autoimmunity. The potential clinical translation of targeted therapy with antigen-specific Tregs is hampered by the difficulties of isolating rare specificities from the natural polyclonal T cell repertoire. Moreover, the initiating antigen is often unknown in autoimmune disease. Here we tested the ability of antigen-specific Tregs generated by retroviral gene transfer to ameliorate arthritis through linked suppression and therefore without cognate recognition of the disease-initiating antigen. We explored two distinct strategies: T cell receptor (TCR) gene transfer into purified CD4+CD25+ T cells was used to redirect the specificity of naturally occurring Tregs; and co-transfer of FoxP3 and TCR genes served to convert conventional CD4+ T cells into antigen-specific regulators. Following adoptive transfer into recipient mice, the gene-modified T cells engrafted efficiently and retained TCR and FoxP3 expression. Using an established arthritis model, we demonstrate antigen-driven accumulation of the gene modified T cells at the site of joint inflammation, which resulted in a local reduction in the number of inflammatory Th17 cells and a significant decrease in arthritic bone destruction. Together, we describe a robust strategy to rapidly generate antigen-specific regulatory T cells capable of highly targeted inhibition of tissue damage in the absence of systemic immune suppression. This opens the possibility to target Tregs to tissue-specific antigens for the treatment of autoimmune tissue damage without the knowledge of the disease-causing autoantigens recognized by pathogenic T cells.
