Effect of thymectomy on human peripheral blood T cell pools in myasthenia gravis
Effect of thymectomy on human peripheral blood T cell pools in myasthenia gravis
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DOI：
10.4049/jimmunol.166.4.2808
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发表时间：
2001-02-15
影响因子：
4.4
通讯作者：
Haynes, BF
中科院分区：
文献类型：
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作者：
Sempowski, GD;Thomasch, JR;Haynes, BF
人类胸腺是胎儿期T细胞库建立所必需的，但出生后胸腺切除术不会导致人类免疫缺陷。由于人类胸腺切除术是为了治疗重症肌无力（MG），我们研究了MG患者胸腺切除术对外周血（PB）幼稚（CD 45 RA（+），CD 62 L（+））和记忆（CD 35 RO（+））T细胞的影响。我们还确定了胸腺切除术对PB细胞水平的影响，PB细胞含有信号联合TCR δ切除环（TRECs），TRECs是一种胸腺移行细胞的分子标记，在离开胸腺后分裂了几次。在胸腺切除术后的不同时间，对17名非胸腺切除和26名胸腺切除的MG患者进行了研究。（1天至41岁），我们发现40岁和80岁之间的PB T细胞TREC水平没有显著的平均差异。然而，胸腺切除和非胸腺切除的MG患者的PB T细胞TREC水平均低于年龄匹配的正常受试者（两者均为p < 0.0001）。这些数据表明，MG本身或治疗MG降低胸腺生成独立于胸腺切除术。其次，为了控制疾病活动和治疗，我们前瞻性地研究了10例MG患者在胸腺切除术前和术后27 - 517天，我们发现胸腺切除术降低了CD 4或CD 8 T细胞TREC浓度，当胸腺切除术前胸腺生成活跃时（6/6例患者），但在胸腺生成最小的患者中几乎没有效果（4/4例患者）。相比之下，胸腺切除术对幼稚PB T细胞的绝对数量没有显著影响。因此，在MG中，切除具有活性胸腺生成的胸腺导致胸腺切除术后PB TREC+ T细胞的显著下降。
The human thymus is required for establishment of the T cell pool in fetal life, but postnatal thymectomy does not lead to immunodeficiency in humans. Because thymectomy in humans is performed for treatment of myasthenia gravis (MG), we have studied patients with MG for effects of thymectomy on peripheral blood (PB) naive (CD45RA(+), CD62L(+)) and memory (CD35RO(+)) T cells. We have also determined the effect of thymectomy on levels of PB cells containing signal joint TCR delta excision circles (TRECs), a molecular marker of thymus emigrants that have divided few times after leaving the thymus, In 17 nonthymectomized and 26 thymectomized MG patients studied at varying times after thymectomy (1 day to 41 years), we found no significant mean difference in PB T cell TREC levels between ages 40 and 80 years. However, both thymectomized and nonthymectomized MG patients had lower PB T cell TREC levels than did age-matched normal subjects (p < 0.0001 for both). These data demonstrated that MG itself or treatment for MG decreased thymopoiesis independent of thymectomy, Next, to control for disease activity and treatment, we prospectively studied, 10 MG patients before and from 27 to 517 days after thymectomy, We found that thymectomy decreased CD4 or CD8 T cell TREC concentrations mast when thymopoiesis was active before thymectomy (six of six patients), but had little effect in patients when thymopoiesis was minimal (four of four patients). In contrast, there was no significant effect of thymectomy on absolute numbers of naive PB T cells. Thus, in MG, removal of a thymus with active thymopoiesis resulted in a significant fall in PB TREC+ T cells postthgmectomy.