Only the CD62L+ subpopulation of CD4+CD25+ regulatory T cells protects from lethal acute GVHD |
| |
Authors: | Ermann Joerg Hoffmann Petra Edinger Matthias Dutt Suparna Blankenberg Francis G Higgins John P Negrin Robert S Fathman C Garrison Strober Samuel |
| |
Institution: | Division of Immunology and Rheumatology, the Department of Medicine, Stanford University School of Medicine, CCSR Bldg, Rm 2215-C, 300 Pasteur Dr, Stanford, CA 94305-5166, USA. |
| |
Abstract: | CD4+CD25+ regulatory T (Treg) cells are potent modulators of alloimmune responses. In murine models of allogeneic bone marrow transplantation, adoptive transfer of donor CD4+CD25+ Treg cells protects recipient mice from lethal acute graft-versus-host disease (aGVHD) induced by donor CD4+CD25- T cells. Here we examined the differential effect of CD62L+ and CD62L- subsets of CD4+CD25+ Treg cells on aGVHD-related mortality. Both subpopulations showed the characteristic features of CD4+CD25+ Treg cells in vitro and did not induce aGVHD in vivo. However, in cotransfer with donor CD4+CD25- T cells, only the CD62L+ subset of CD4+CD25+ Treg cells prevented severe tissue damage to the colon and protected recipients from lethal aGVHD. Early after transplantation, a higher number of donor-type Treg cells accumulated in host mesenteric lymph node (LN) and spleen when CD4+CD25+CD62L+ Treg cells were transferred compared with the CD62L- subset. Subsequently, CD4+CD25+CD62L+ Treg cells showed a significantly higher capacity than their CD62L- counterpart to inhibit the expansion of donor CD4+CD25- T cells. The ability of Treg cells to efficiently enter the priming sites of pathogenic allo-reactive T cells appears to be a prerequisite for their protective function in aGVHD. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
| 点击此处可从《Blood》浏览原始摘要信息 |
| 点击此处可从《Blood》下载免费的PDF全文 |
|