Département de Biothérapie, Centre d'Investigation Clinique intégré en Biothérapies, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; INSERM UMR1163, Paris, France.
Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Paris, France; Unité d'Immunologie-Hématologie et Rhumatologie Pédiatrique, Hôpital Necker-Enfants Malades, AP-HP, Paris, France; INSERM UMR1163, Paris, France.
J Allergy Clin Immunol. 2015 May;135(5):1303-9.e1-3. doi: 10.1016/j.jaci.2014.08.019. Epub 2014 Oct 3.
Combined immunodeficiencies (CIDs) form a heterogeneous group of inherited conditions that affect the development, function, or both of T cells. The treatment of CIDs with allogeneic hematopoietic stem cell transplantation (HSCT) is complicated by a high incidence of life-threatening infections and an increased risk of graft-versus-host disease (GVHD).
In view of the growing evidence that alloreactivity is mainly derived from human naive T cells, the selective depletion of naive T cells from allografts might constitute a way of reducing alloreactivity while maintaining memory T-cell responsiveness to pathogens.
Five consecutive patients with CIDs and chronic viral infections underwent an allogeneic, HLA-mismatched HSCT. Given the patients' infection status and the potential risk of severe GVHD in the mismatched setting, the CD34(-) fraction of the allograft was depleted of naive T cells by using magnetic CD45RA beads.
Engraftment occurred in 4 of the 5 patients. No severe GVHD occurred. In the 4 engrafted patients viral infections were cleared within 2 months of the HSCT, and both cellular and humoral immunity were re-established within a year of the HSCT. An early T-cell response against viral pathogens was documented in 2 patients.
The present pilot study shows that clinical-grade depletion of naive T cells from an allograft through the use of magnetic CD45RA beads seems to be a feasible and efficacious option for the treatment of patients with CIDs at high risk of GVHD, infection, or both in an HLA-mismatched setting.
联合免疫缺陷（CIDs）形成了一组异质性的遗传性疾病，这些疾病会影响 T 细胞的发育、功能或两者兼而有之。异基因造血干细胞移植（HSCT）治疗 CIDs 存在严重威胁生命的感染发生率高和移植物抗宿主病（GVHD）风险增加等问题。
鉴于越来越多的证据表明同种异体反应主要来源于人类幼稚 T 细胞，因此从同种异体移植物中选择性耗尽幼稚 T 细胞可能是一种降低同种异体反应性同时保持记忆 T 细胞对病原体反应性的方法。
5 例连续 CIDs 合并慢性病毒感染患者接受异基因、HLA mismatched HSCT。鉴于患者的感染状态和不匹配情况下发生严重 GVHD 的潜在风险，使用磁性 CD45RA 珠从移植物的 CD34(-) 部分耗竭幼稚 T 细胞。
5 例患者中有 4 例发生移植物嵌合。未发生严重 GVHD。在 4 例植入患者中，病毒感染在 HSCT 后 2 个月内清除，细胞和体液免疫在 HSCT 后 1 年内重建。在 2 例患者中记录到针对病毒病原体的早期 T 细胞反应。
本初步研究表明，临床级别的通过使用磁性 CD45RA 珠从同种异体移植物中耗尽幼稚 T 细胞，对于 HLA 不匹配环境中高风险发生 GVHD、感染或两者兼有的 CIDs 患者的治疗似乎是一种可行且有效的选择。
