J mmunol：调节性T细胞可预测骨髓增生异常综合征

Moffitt癌症中心研究人员发现，记忆调节性T细胞物理特性的变化可以预测骨髓增生异常综合征（MDS）发展成急性髓细胞性白血病的风险，这一发现可能改善MDS患者的预测，同时也有助于开发更好的治疗手段。

这项研究发表在Journal of Immunology杂志上。骨髓增生异常综合征是起源于造血干细胞的一组异质性髓系克隆性疾病，特点是髓系细胞分化及发育异常，表现为无效造血、难治性血细胞减少、造血功能衰竭，高风险向急性髓系白血病（AML）转化。

三分之一的MDS患者会出现骨髓造血功能衰竭，并在确诊后的最初几年内演变成急性髓系白血病。MDS患者骨髓中产生的血细胞是无效的，这常常使得患者贫血，需要频繁输血。

这种疾病可能是由于癌症化疗治疗或放疗导致的结果，或者与骨髓故障导致的频繁输血以及随后的铁超负荷造成的。反复输血往往会造成铁的积累，而患者身体中用来减少铁积累的机制缺乏，病人的器官往往铁超负荷，导致心脏衰竭、肝损伤，出现对感染的易感性和其他并发症。骨髓移植可能是MDS患者往往必须采取的治疗策略。为了了解更多关于MDS疾病的发展，Moffitt的研究人员重点研究免疫系统，特别是被称为调节性T细胞在骨髓增生异常综合征中的作用。

研究人员说，调节性T细胞在实体瘤的肿瘤免疫入侵中发挥重要作用，但很少有人知道调节性T细胞在癌前病变中所发挥的作用。免疫学系Pearlie K. Epling药学博士说： 我们重点研究了被称为记忆调节性T细胞的调节性T细胞亚群。

研究发现，MDS患者记忆调节性T细胞发生了物理特性的变化或表型的变化，这提示它们可能会以与效应记忆性Ť细胞激活相似的方式激活。通过观察病人的效应记忆调节性T细胞，我们能够确定MDS患者疾病的进展，预测发展成急性髓细胞性白血病的风险。研究人员说，效应记忆调节性T细胞的增加可能反映了免疫抑制效应的激活，并可能是预示患者免疫微环境转换的最早生物标志物。

doi:10.4049/jimmunol.1200602
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Expansion of Effector Memory Regulatory T Cells Represents a Novel Prognostic Factor in Lower Risk Myelodysplastic Syndrome

Adam W. Mailloux, Chiharu Sugimori, Rami S. Komrokji, Lili Yang, et al.

Myelodysplastic syndromes are premalignant diseases characterized by cytopenias, myeloid dysplasia, immune dysregulation with association to autoimmunity, and variable risk for acute myeloid leukemia transformation. Studies of FOXP3⁺ regulatory T cells (Tregs) indicate that the number and/or activation state may influence cancer progression in these patients. Focusing on patients with a lower risk for leukemia transformation, 18 (34.6%) of 52 patients studied displayed an altered Treg compartment compared with age-matched controls. Delineation of unique Treg subsets revealed that an increase in the absolute number of CD4⁺FOXP3⁺CD25⁺CD127^lowCD45RA⁻CD27⁻ Tregs (effector memory Tregs [Treg^EM]) was significantly associated with anemia (p = 0.046), reduced hemoglobin (p = 0.038), and blast counts ≥5% (p = 0.006). In healthy donors, this Treg^EM population constitutes only 2% of all Tregs (one to six Tregs per microliter) in peripheral blood but, when isolated, exhibit greater suppressive activity in vitro. With a median follow-up of 3.1 y (range 2.7–4.9 y) from sample acquisition, increased numbers of Treg^EM cells proved to have independent prognostic importance in survival estimates, suggesting that enumeration of this Treg subset may be a more reliable indicator of immunological escape than FOXP3⁺ T cells as a whole. Based on multivariate analyses, Treg^EM impacted survival independently from myeloblast characteristics, cytopenias, karyotype, and comorbidities. Based on these findings, Treg^EM cell expansion may be synonymous with human Treg activation and indicate microenvironmental changes conducive to transformation in myelodysplastic syndromes.