Loading...
Please wait, while we are loading the content...
Similar Documents
Protection from lethal murine graft-versus-host disease without compromise of alloengraftment using transgenic donor T cells expressing a thymidine kinase suicide gene.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Drobyski, William R. Morse, Herbert C. Burns, William H. Casper, James T. Sandford, Gordon |
| Copyright Year | 2001 |
| Abstract | Donor T cells play a pivotal role in facilitating alloengraftment but also cause graft-versus-host disease (GVHD). Ex vivo T-cell depletion (TCD) of donor marrow is the most effective strategy for reducing GVHD but can compromise engraftment. This study examined an approach whereby donor T cells are selectively eliminated in vivo after transplantation using transgenic mice in which a thymidine kinase (TK) suicide gene is targeted to the T cell using a CD3 promoter/enhancer construct. Lethally irradiated B10.BR mice transplanted with major histocompatibility complex (MHC)-incompatible TCD C57BL/6 (B6) bone marrow (BM) plus TK(+) T cells were protected from GVHD after treatment with ganciclovir (GCV) in a schedule-dependent fashion. To examine the effect of GCV treatment on alloengraftment, sublethally irradiated AKR mice underwent transplantation with TCD B6 BM plus limiting numbers (5 x 10(5)) of B6 TK(+) T cells. Animals treated with GCV had comparable donor engraftment but significantly reduced GVHD when compared with untreated mice. These mice also had a significantly increased number of donor splenic T cells when assessed 4 weeks after bone marrow transplantation. Thus, the administration of GCV did not render recipients T-cell deficient, but rather enhanced lymphocyte recovery. Adoptive transfer of spleen cells from GCV-treated chimeric mice into secondary AKR recipients failed to cause GVHD indicating that donor T cells were tolerant of recipient alloantigens. These studies demonstrate that administration of TK gene-modified donor T cells can be used as an approach to mitigate GVHD without compromising alloengraftment. |
| File Format | PDF HTM / HTML |
| DOI | 10.1182/blood.V97.8.2506 |
| PubMed reference number | 11290616 |
| Journal | Medline |
| Volume Number | 97 |
| Issue Number | 8 |
| Alternate Webpage(s) | http://www.bloodjournal.org/content/bloodjournal/97/8/2506.full.pdf?sso-checked=true |
| Journal | Blood |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
