Lymphadenectomy prior to rat hind limb allotransplantation prevents graft-versus-host disease in chimeric hosts.
In previous rat studies, the use of mixed allogeneic chimerism (MAC) to induce host tolerance to hind limb allografts has resulted in severe graft-versus-host disease (GVHD). The purpose of this study was to determine if immunocompetent cells in bone marrow (BM) and/or lymph nodes (LNs) of transplanted limbs were responsible for inducing GVHD in mixed chimeric hosts. [ACI-->Wistar Furth] chimeric rats received ACI hind limbs that were non-irradiated, irradiated (1050 cGy) or lymphadenectomized. Rejection, GVHD and donor chimerism was assessed. Chimeric hosts rejected none of their limbs. However, hosts of non-irradiated hind limbs succumbed to GVHD 22.4+/-0.8 days after transplantation. In contrast, chimeras that received irradiated or lymphadenectomized ACI hind limbs showed no clinical or histological signs of GVHD at 5 months. We conclude that mixed chimeric hosts are susceptible to GVHD due to the immunocompetent cell load provided by the LNs, not the BM, of hind limb allografts.
Brouha
Pascal C R
PC
Surgery Department, University of Louisville, 320 MDR Building, 511 S. Floyd Street, Louisville, Kentucky, USA.
Perez-Abadia
Gustavo
G
Francois
Cedric G
CG
Laurentin-Perez
Luis A
LA
Gorantla
Vijay
V
Vossen
Marieke
M
Tai
Chau
C
Pidwell
Diane
D
Anderson
Gary L
GL
Stadelmann
Wayne K
WK
Hewitt
Charles W
CW
Kon
Moshe
M
Barker
John H
JH
Maldonado
Claudio
C
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000528:radiation effects; D002678:Chimera; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D006614:Hindlimb / Q000637:transplantation*; D007108:Immune Tolerance; D008197:Lymph Node Excision; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000166:cytology / Q000528:radiation effects; D008297:Male; D051381:Rats; D011912:Rats, Inbred ACI; D011920:Rats, Inbred WF; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation