Memory CD4+ T cells do not induce graft-versus-host disease.
Memory CD4+ T cells do not induce graft-versus-host disease.
复制标题
DOI：
10.1172/jci17601
复制
发表时间：
2003-07
期刊：
影响因子：
--
通讯作者：
Britt E. Anderson;J. McNiff;Jun Yan;H. Doyle;M. Mamula;M. Shlomchik;W. Shlomchik
中科院分区：
文献类型：
--
作者：
Britt E. Anderson;J. McNiff;Jun Yan;H. Doyle;M. Mamula;M. Shlomchik;W. Shlomchik
移植物抗宿主病（GVHD）仍然是异基因干细胞移植（alloSCT）中发病率和死亡率的主要原因。伴随干细胞移植的供体T细胞通过攻击受体组织引起GVHD;因此，所有患者都通过从同种异体移植物中耗尽T细胞或通过免疫抑制剂药物来接受GVHD预防。除了提供移植物抗白血病效应外，供体T细胞对于重建T细胞介导的免疫力至关重要。理想情况下，对感染因子的免疫力将从供体转移到宿主而没有GVHD。大多数供体都暴露于常见的病原体，并且具有针对病原性抗原的记忆T细胞的前体频率增加。因此，我们询问记忆性CD62L-CD44 + CD4 + T细胞是否比未分级或幼稚CD4 + T细胞诱导更少的GVHD。引人注目的是，我们发现记忆性CD4细胞既不诱导临床也不诱导组织学GVHD。这种效应不是由于在CD62L-CD44+部分中发现的CD4 + CD25+调节性T细胞的数量增加，因为这些细胞的记忆T细胞消耗不会引起GVHD。记忆性CD4细胞在体内和体外植入并对抗原产生应答。如果这些小鼠结果适用于人类alloSCT，那么选择性给予记忆T细胞可以大大改善移植后免疫重建。
Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic stem cell transplantation (alloSCT). Donor T cells that accompany stem cell grafts cause GVHD by attacking recipient tissues; therefore, all patients receive GVHD prophylaxis by depletion of T cells from the allograft or through immunosuppressant drugs. In addition to providing a graft-versus-leukemia effect, donor T cells are critical for reconstituting T cell-mediated immunity. Ideally, immunity to infectious agents would be transferred from donor to host without GVHD. Most donors have been exposed to common pathogens and have an increased precursor frequency of memory T cells against pathogenic antigens. We therefore asked whether memory CD62L-CD44+ CD4+ T cells would induce less GVHD than unfractionated or naive CD4+ T cells. Strikingly, we found that memory CD4 cells induced neither clinical nor histologic GVHD. This effect was not due to the increased number of CD4+CD25+ regulatory T cells found in the CD62L-CD44+ fraction because memory T cells depletion of these cells did not cause GVHD. Memory CD4 cells engrafted and responded to antigen both in vivo and in vitro. If these murine results are applicable to human alloSCT, selective administration of memory T cells could greatly improve post-transplant immune reconstitution.