Peripheral regulation of graft-versus-host alloreactivity in mixed chimeric miniature swine.
BACKGROUND
Despite the presence of circulating donor-derived T cells during the induction of mixed chimerism across MHC barriers in miniature swine, severe graft-versus-host disease was avoided in the majority of animals. In this study, we investigated the possible roles of recipient and donor lymphoid populations in the regulation of donor-anti-recipient alloreactivity.


METHODS
Mixed chimerism across a full MHC-mismatch barrier was established in miniature swine using a high-dose allogeneic peripheral blood stem cell protocol. Peripheral blood mononuclear cells from mixed chimeric swine were co-cultured with naïve donor-matched responders and naïve recipient-matched stimulators in mixed lymphocyte reactions.


RESULTS
Peripheral blood mononuclear cells from mixed chimeras inhibited donor-anti-recipient proliferation. This suppression was radioresistant to 25 Gy. Suppression of donor-anti-recipient alloreactivity was not observed in mixed lymphocyte co-cultures when donor-derived cells were added in the absence of recipient-derived cells.


CONCLUSIONS
These results suggest an association between the presence of an active and relatively radioresistant cell population, demonstrable in vitro, and the regulation of graft-versus-host disease across MHC barriers in mixed chimeric miniature swine.
Kunisaki
S M
SM
Transplantation Biology Research Center, Massachusetts General Hospital, MGH-East, Building 149-9019, 13th Street, Boston, MA 02129, USA.
Haller
G W
GW
Fuchimoto
Y
Y
Huang
C A
CA
Sachs
D H
DH
D000818:Animals; D002678:Chimera; D006087:Graft vs Host Reaction; D007519:Isoantigens / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000502:physiology; D013552:Swine; D013556:Swine, Miniature; D014019:Tissue Donors
D007519:Isoantigens