Suppression of disease in New Zealand Black/New Zealand White lupus-prone mice by adoptive transfer of ex vivo, expanded regulatory T cells
Suppression of disease in New Zealand Black/New Zealand White lupus-prone mice by adoptive transfer of ex vivo, expanded regulatory T cells
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DOI：
10.4049/jimmunol.177.3.1451
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发表时间：
2006-08-01
影响因子：
4.4
通讯作者：
Daikh, David I.
中科院分区：
文献类型：
--
作者：
Scalapino, Kenneth J.;Tang, Qizhi;Daikh, David I.
越来越多的研究表明，具有调节能力的CD 4（+）T细胞亚群（调节性T细胞; T-T细胞）可以控制器官特异性自身免疫性疾病。为了确定胸腺来源的T-reg异常是否在系统性红斑狼疮中发挥作用，我们评估了（新西兰黑X新西兰白色）F-1（B/W）狼疮易感小鼠中T-reg的患病率和功能。为了探索T-g抑制疾病的潜力，我们评估了过继转移纯化的、离体扩增的胸腺衍生的T-g对肾脏疾病进展的影响。我们发现，尽管与年龄匹配的非自身免疫小鼠相比，在患病前的B/W小鼠的局部淋巴结和脾脏中THBE的患病率降低，但这些细胞在老年患病小鼠中的数量增加。此外，这些细胞在体外增殖的能力与从非自身免疫对照动物中纯化的那些细胞相当。将纯化的CD 4（+）CD 25（+）CD 62 L（高）B/W T-T细胞体外扩增80倍，产生具有稳定抑制表型的细胞。这些外源性扩增细胞的连续转移降低了小鼠发生肾脏疾病的速度;在治疗动物发生蛋白尿后进行第二次转移进一步减缓了肾脏疾病的进展，并显着提高了生存率。这些研究表明，胸腺衍生的T细胞可能在控制狼疮倾向的B/W小鼠的自身免疫中具有重要作用，并且这些细胞的扩增可能构成系统性红斑狼疮的新的治疗方法。
An increasing number of studies indicate that a subset of CD4(+) T cells with regulatory capacity (regulatory T cells; T-regs) can function to control organ-specific autoimmune disease. To determine whether abnormalities of thymic-derived T,,g, play a role in systemic lupus erythematosus, we evaluated T-reg prevalence and function in (New Zealand Black X New Zealand White)F-1 (B/W) lupus-prone mice. To explore the potential of T-g to suppress disease, we evaluated the effect of adoptive transfer of purified, ex vivo expanded thymic-derived T-regs on the progression of renal disease. We found that although the prevalence of Tregs is reduced in regional lymph nodes and spleen of prediseased B/W mice compared with age-matched non-autoimmune mice, these cells increase in number in older diseased mice. In addition, the ability of these cells to proliferate in vitro was comparable to those purified from non-autoimmune control animals. Purified CD4(+)CD25(+)CD62L(high) B/W T-regs were expanded ex vivo 80-fold, resulting in cells with a stable suppressor phenotype. Adoptive transfer of these exogenously expanded cells reduced the rate at which mice developed renal disease; a second transfer after treated animals had developed proteinuria further slowed the progression of renal disease and significantly improved survival. These studies indicate that thymic-derived T-regs may have a significant role in the control of autoimmunity in lupus-prone B/W mice, and augmentation of these cells may constitute a novel therapeutic approach for systemic lupus erythematosus.