Alpha beta TCR+ T cells play a nonredundant role in the rejection of heart allografts in mice.
BACKGROUND
Although the transplantation of solid organs and cellular grafts is a clinical routine, the morbidity and mortality associated with immunosuppression is significant. This could be avoided by the induction of donor-specific tolerance. To develop targeted antirejection strategies and regimens to induce donor-specific tolerance, cell populations in the recipient-mediating rejection of solid organ and cellular grafts must be defined. In this study we examined the role of alpha beta-TCR+ cells in the rejection of allogeneic heart grafts, by use of knockout (KO) mice deficient in the production of alpha beta-TCR+ T cells.


METHODS
C57BL/6-TcrbtmlMom (alpha beta-KO) and C57BL6/J (B6) recipient mice were transplanted with B10.BR/SgSnJ (B10.BR) or BALB/c heart allografts. Animals also received bone marrow from normal B10.BR donors, followed by donor-specific or third-party heart transplants.


RESULTS
Naive B6 control mice rejected B10.BR and BALB/c grafts within 16 days. In striking contrast, B10.BR and BALB/c heart allografts were indefinitely accepted in unmanipulated alpha beta-KO mice. The immune responsiveness was restored after bone marrow transplantation from normal donors. After bone marrow transplantation major histocompatibility-disparate BALB/c third-party heart grafts were rejected, whereas donor-specific grafts were still accepted.


CONCLUSIONS
alpha beta-TCR+ T cells play a nonredundant role in the rejection of heart allografts in mice. Bone marrow chimerism is associated with donor-specific transplantation tolerance.
Exner
B G
BG
Institute for Cellular Therapeutics, University of Louisville, Glenolden, Pa. 19036, USA.
Que
X
X
Mueller
Y M
YM
Domenick
M A
MA
Neipp
M
M
Ildstad
S T
ST
D000818:Animals; D016026:Bone Marrow Transplantation; D006084:Graft Rejection / Q000209:etiology*; D016027:Heart Transplantation / Q000276:immunology*; D007108:Immune Tolerance; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*; D014184:Transplantation, Homologous
D016693:Receptors, Antigen, T-Cell, alpha-beta