Altered naive and memory CD4+ T-cell homeostasis and immunosenescence characterize younger patients with myelodysplastic syndrome.
Altered naive and memory CD4+ T-cell homeostasis and immunosenescence characterize younger patients with myelodysplastic syndrome.
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幼稚和记忆的改变CD4+ T细胞稳态和免疫衰老的特征是年轻的骨髓增生综合征。
作者：
年轻骨髓增生异常综合征（MDS）患者对免疫抑制治疗（IST）的反应与损害造血的T细胞主导的自身免疫过程有关。对76例MDS患者和54例健康对照者年龄校正后的CD4：CD8比值进行分析，结果显示，在包括国际预后评分系统定义的低风险和高风险MDS患者的一组中，CD4+不足而不是CD8+ T细胞扩增与较低的比值相关。在年轻的MDS患者中，由CD45RA和CD62L显示定义的幼稚和记忆表型显示幼稚CD4+和CD8+ T细胞耗竭，表明可能与IST反应性相关。为了确定T细胞亚群分布、T细胞更新和自身免疫之间的相关性，对20例患者在IST前后进行了研究。在IST应答患者中，CD4：CD8比值与治疗前的增殖性T细胞指数呈负相关，表明增殖可能与加速的CD4+ T细胞更新和造血功能衰竭有关。我们的数据显示了开创性的发现，即在MDS中CD4+和CD8+ T细胞亚群均失调。这些T细胞缺陷和对IST的反应之间的关联表明，异常的T细胞稳态和慢性激活是影响年轻患者自身免疫性造血抑制的关键决定因素。
Response to immunosuppressive therapy (IST) in younger patients with myelodysplastic syndrome (MDS) has been linked to a T-cell-dominant autoimmune process that impairs hematopoiesis. Analysis of the age-adjusted CD4:CD8 ratio in 76 MDS patients compared with 54 healthy controls showed that inadequate CD4+, rather than expansion of CD8+ T cells, was associated with a lower ratio in a group that included both lower and higher risk MDS patients defined by the International Prognostic Scoring System. In younger MDS patients, naive and memory phenotypes defined by CD45RA and CD62L display showed depletion of naive CD4+ and CD8+ T cells, suggesting a possible relationship to IST responsiveness. To determine the correlation between T-cell subset distribution, T-cell turnover and autoimmunity, a cohort of 20 patients were studied before and after IST. The CD4:CD8 ratio correlated inversely with the proliferative T-cell index before treatment in IST-responsive patients, suggesting that proliferation may be linked to accelerated CD4+ T-cell turnover and hematopoietic failure. Our data show seminal findings that both CD4+ and CD8+ T-cell subsets are dysregulated in MDS. Association between these T-cell defects and response to IST suggests that aberrant T-cell homeostasis and chronic activation are critical determinants influencing autoimmune hematopoietic suppression in younger patients.