Mixed xenogeneic chimeras (rat + mouse to mouse). Evidence of rat stem cell engraftment, strain-specific transplantation tolerance, and skin-specific antigens.
We report the induction of stable and reliably detectable mixed xenogeneic chimerism through the coadministration of a mixture of untreated rat bone marrow plus T cell-depleted mouse bone marrow into B10 recipients conditioned with total body irradiation (TCD B10 mouse + untreated F344 rat----B10 mouse). Recipients repopulated as true mixed lymphopoietic chimeras, with from 1-21.6% rat-derived lymphoid cells in peripheral blood and splenic lymphoid tissue. Production of rat platelets was also demonstrated. Rat platelet and lymphoid chimerism was reliably detectable in chimeras from 1 to 7 months following reconstitution, suggesting engraftment of the rat bone marrow stem cell. Production of each stem cell-derived lineage appeared to be under independent regulation since a significantly greater proportion of platelets were rat-derived (24-81%) than were lymphocytes (1-21.6% rat), while erythrocytes were preferentially syngeneic (less than 2% rat). The tolerance induced by this model was highly donor strain-specific: donor-specific rat and mouse skin grafts were accepted while MHC-disparate third-party mouse (C3H; H-2k) and rat (Wistar Furth; Rt1Au) skin grafts were promptly rejected. Although specifically prolonged xenogeneic donor rat skin grafts underwent a slow chronic rejection, and some totally disappeared. In spite of this, chimeras retained their lymphoid chimerism, suggesting the presence of skin-specific antigens. This model for mixed xenogeneic chimerism with reliably detectable rat lymphoid cells may provide a model to study the existence of tissue-specific antigens across a species barrier, as well as mechanisms responsible for the induction and maintenance of this strain-specific transplantation tolerance.
Ildstad
S T
ST
Department of Surgery, Pittsburgh Cancer Institute, University of Pittsburgh, PA 15261.
Boggs
S S
SS
Vecchini
F
F
Wren
S M
SM
Hronakes
M L
ML
Johnson
P C
PC
Van den Brink
M R
MR
D000818:Animals; D000941:Antigens / Q000276:immunology*; D016026:Bone Marrow Transplantation; D002678:Chimera; D005434:Flow Cytometry; D006085:Graft Survival; D007108:Immune Tolerance; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000276:immunology*; D016038:Skin Transplantation; D013045:Species Specificity; D013601:T-Lymphocytes / Q000502:physiology; D014183:Transplantation, Heterologous
D000941:Antigens