Tolerance induction by third-party "off-the-shelf" CD4+CD25+ Treg cells.
OBJECTIVE
Recent reports have shown that donor or host CD4(+)CD25(+) Treg cells can be used to control GVHD or graft rejection following allogeneic BMT in mice. In the present study we investigated the potential of third-party Treg cells compared to donor-type cells to facilitate BM allografting.


METHODS
Graft rejection is assessed in a mouse model of T cell-mediated BM allograft rejection. Lethally irradiated C3H mice are transplanted at day 2 after irradiation with T cell-depleted Balb/Nude BM. Graft rejection is induced by purified host-type T cells infused one day prior to BMT. Cells tested for their facilitating activity are added to the T cell-depleted BM allograft.


RESULTS
Naïve or ex vivo-expanded third-party Treg cells can effectively enhance engraftment of T cell-depleted BM allografts, exhibiting reactivity in vitro and in vivo similar to that found for donor-type Treg cells.


CONCLUSIONS
The use of third-party Treg cells in contrast to donor-type cells could allow advanced preparation of a large bank of Treg cells (off-the-shelf), with all the appropriate quality controls required for cell therapy.
Steiner
David
D
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Brunicki
Noga
N
Blazar
Bruce R
BR
Bachar-Lustig
Esther
E
Reisner
Yair
Y
D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D020123:Sirolimus / Q000008:administration & dosage; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D018183:Transplantation Chimera; D014181:Transplantation Immunology / Q000276:immunology; D023001:Transplantation Tolerance / Q000187:drug effects / Q000528:radiation effects; D014184:Transplantation, Homologous / Q000009:adverse effects
D020123:Sirolimus