Prevention of graft-versus-host disease by intra-bone marrow injection of donor T cells.
We have recently found that intra-bone marrow-bone marrow transplantation (IBM-BMT) can be used to prevent graft-versus-host disease (GvHD), even when intensive donor lymphocyte infusion (DLI) is carried out. In the present study, in conjunction with IBM-BMT, allogeneic splenic T cells as DLI were also injected into the bone marrow cavity of lethally irradiated (8.5 Gy) recipients. The extent of GvHD was compared with that of recipients that had received allogeneic IBM-BMT plus i.v. injection of allogeneic T cells (intravenous DLI [IV-DLI]). GvHD in recipients treated with allogeneic IBM-BMT plus IBM-DLI was far milder than in those treated with allogeneic IBM-BMT plus IV-DLI. This was confirmed macroscopically and histopathologically. The frequency of regulatory T cells (Tregs) detected as CD4(+)CD25(+) and CD4(+)Foxp3(+) cells was significantly higher in recipients treated with IBM-BMT plus IBM-DLI than in those treated with IBM-BMT plus IV-DLI. Donor-derived helper T (Th) cells polarized to Th2 type in recipients treated with IBM-BMT plus IBM-DLI, whereas Th1 cells were dominant in recipients treated with IBM-BMT plus IV-DLI. Furthermore, the production of transforming growth factor-beta and hepatocyte growth factor from bone marrow stromal cells was enhanced after IBM-DLI. Thus, IBM-BMT plus IBM-DLI seem to preferentially induce Tregs and Th2, resulting in the prevention of GvHD. Disclosure of potential conflicts of interest is found at the end of this article.
Fukui
Junichi
J
First Department of Pathology, Kansai Medical University, Fumizono-cho, Moriguchi City, Osaka, Japan.
Inaba
Muneo
M
Ueda
Yusuke
Y
Miyake
Takashi
T
Hosaka
Naoki
N
Kwon
A-Hon
AH
Sakaguchi
Yutaku
Y
Tsuda
Masanobu
M
Omae
Mariko
M
Kamiyama
Yasuo
Y
Ikehara
Susumu
S
D000818:Animals; D001835:Body Weight; D001853:Bone Marrow / Q000473:pathology*; D016026:Bone Marrow Transplantation / Q000379:methods; D002470:Cell Survival; D006086:Graft vs Host Disease / Q000473:pathology / Q000517:prevention & control*; D017148:Infusions, Intraosseous; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017154:Stromal Cells / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology / Q000637:transplantation*; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods*