The recovery of resistance to alloengraftment following lethal irradiation and administration of T cell-depleted syngeneic bone marrow.
Recent studies from this laboratory have shown that unmanipulated, MHC-mismatched allogeneic bone marrow (BM) engrafts and produces complete allogeneic chimerism when administered to recipient mice 8 days following lethal irradiation and reconstitution with T cell-depleted (TCD) syngeneic bone marrow. Host lymphopoietic recovery thus appears to be insufficient by 8 days after irradiation and TCD syngeneic bone marrow transplantation (BMT) to resist alloengraftment. In the present studies we have examined the development of such resistance to alloengraftment by determining the limits of the time period permitting engraftment, and have assessed the role of allogeneic T cells in achieving chimerism after delayed allogeneic bone marrow transplantation. Our results indicate that increasing the delay for more than 8 days following irradiation and TCD syngeneic BMT leads to a rapid loss of the ability to achieve alloengraftment by non-TCD allogeneic bone marrow. Removal of T cells from allogeneic BM inocula administered 8 days after irradiation and TCD syngeneic BMT resulted in loss of the ability to achieve alloengraftment. Repopulation patterns in host spleens following delayed reconstitution suggest that active elimination of engrafted syngeneic lymphohemopoietic elements is necessary to permit engraftment of allogeneic marrow administered after such a delay.
Chester
C H
CH
Transplantation Biology Section, National Cancer Institute, Bethesda, Maryland 20892.
Sykes
M
M
Sachs
D H
DH
D000818:Animals; D001853:Bone Marrow / Q000276:immunology / Q000502:physiology; D016026:Bone Marrow Transplantation; D006085:Graft Survival; D007108:Immune Tolerance; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D011828:Radiation Chimera; D016038:Skin Transplantation; D013154:Spleen / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes; D013997:Time Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic