Broers Annoek E C, Bruinsma Marieke, Posthumus-van Sluijs Sandra J, Wils Evert-Jan, Spits Hergen, Löwenberg Bob, Braakman Eric, Cornelissen Jan J
Department of Hematology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
Haematologica. 2007 Aug;92(8):1099-106. doi: 10.3324/haematol.10625.
Interleukin-7 (IL-7) has been studied for its possible immunorestorative capacities following stem cell transplantation and has been shown to enhance post-transplant immune recovery predominantly by peripheral T-cell expansion. A major concern of IL-7 is its possible aggravating effect on graft-versus-host and host-versus-graft reactivity.
To study the effect of IL-7 on host-versus-graft reactivity, we applied IL-7 in an experimental transplantation model using RAG-1-/- mice supplied with B6 CD45.1 congenic T cells as recipients of T-cell depleted allogeneic bone marrow grafts.
Rejection of minor antigen-mismatched bone marrow was significantly reduced in IL-7 treated recipients compared with PBS treated control mice. Rejection was observed in 2 out of 18 IL-7 treated mice compared with 9 out of 17 PBS treated mice (11% vs. 53%; p=0.012). IL-7 administration resulted in enhanced recovery of peripheral blood CD4+CD25+ regulatory T cells (Treg) with a concomitant increase in peripheral blood Foxp3 mRNA expression. IL-7Ra (CD127) was expressed by the vast majority of CD4+Foxp3+ T cells. The incidence of graft rejection following fully MHC mismatched bone marrow transplantation was not reduced nor enhanced by IL-7 administration.
Post-transplant IL-7 administration protects against minor antigen-mismatched bone marrow rejection, which may be due to enhanced Treg recovery.
白细胞介素-7（IL-7）已被研究其在干细胞移植后可能的免疫恢复能力，并且已显示主要通过外周T细胞扩增来增强移植后的免疫恢复。IL-7的一个主要问题是其对移植物抗宿主和宿主抗移植物反应性可能的加重作用。
为研究IL-7对宿主抗移植物反应性的影响，我们在一个实验性移植模型中应用IL-7，该模型使用供应有B6 CD45.1同基因T细胞的RAG-1-/-小鼠作为去除T细胞的异基因骨髓移植的受体。
与用PBS处理的对照小鼠相比，接受IL-7处理的受体中次要抗原错配骨髓的排斥反应显著降低。18只接受IL-7处理的小鼠中有2只出现排斥反应，而17只接受PBS处理的小鼠中有9只出现排斥反应（11%对53%；p=0.012）。给予IL-7导致外周血CD4+CD25+调节性T细胞（Treg）恢复增强，同时外周血Foxp3 mRNA表达增加。绝大多数CD4+Foxp3+ T细胞表达IL-7Ra（CD127）。给予IL-7对完全MHC错配骨髓移植后的移植物排斥发生率没有降低也没有增强。
移植后给予IL-7可预防次要抗原错配骨髓排斥，这可能是由于Treg恢复增强所致。
