改造人體防御系統(tǒng)中的調(diào)節(jié)性細(xì)胞有可能讓科學(xué)家使用有針對(duì)性的方式抑制一種過度活躍的自體免疫應(yīng)答并減少對(duì)抑制整個(gè)免疫系統(tǒng)的藥物的需求。
Hans Stauss及其同事調(diào)查了設(shè)計(jì)有能力減少炎癥而不論最初引發(fā)因素是什么的調(diào)節(jié)性T細(xì)胞的兩種策略,。在一組實(shí)驗(yàn)室實(shí)驗(yàn)中,，這組科學(xué)家使用基因轉(zhuǎn)移從而制造出了具有特異性的調(diào)節(jié)性T細(xì)胞。對(duì)于第二組,，這組科學(xué)家轉(zhuǎn)換了正常T細(xì)胞的特異性并讓它們具有了調(diào)節(jié)功能,。這組科學(xué)家然后利用一種小鼠關(guān)節(jié)炎模型研究了這種改造后的調(diào)節(jié)性T細(xì)胞的免疫抑制效果，在實(shí)驗(yàn)中,，科學(xué)家把這些細(xì)胞靜脈注射到了這些小鼠體內(nèi),。這種改造后的調(diào)節(jié)性T細(xì)胞在關(guān)節(jié)炎的位置積聚。在那里,，這些細(xì)胞抑制了炎癥和骨損壞,。這組作者說,，這種改造過程的速度以及這種細(xì)胞減少身體炎癥反應(yīng)的能力讓這種方法有潛力用于一大批目前依賴于全身免疫抑制療法的自體免疫疾病。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
