An absence of T cells in murine bone marrow allografts leads to an increased susceptibility to rejection by natural killer cells and T cells.
The mechanisms behind the increased incidence of marrow graft failure in recipients that receive allogeneic marrow depleted of T cells were studied. Recipient mice were lethally irradiated and challenged with bone marrow cells (BMC) from C.B-17 +/+ (+/+) donors. Radioisotope 125IUdR incorporation was assessed 5 to 7 days after transfer to determine the extent of engraftment. Some groups received BMC in which the T cells were removed by treatment with antibody and C. In addition, some groups received BMC from T cell-deficient C.B-17 scid/scid (SCID) mice to determine the postulated need for donor T cells in hematopoiesis and engraftment. In a model system that distinguishes between possible host NK cell and radioresistant T cell-mediated rejection of marrow allografts, it was determined that the absence of donor T cells in a marrow graft does not affect engraftment in syngeneic recipients. However, both host NK cell and radioresistant T cell rejection was markedly enhanced when SCID BMC or BMC from C.B-17 +/+ donors that had T cells removed by antibody and complement were infused into irradiated allogeneic recipients. Furthermore, the addition of alloreactive thymocytes as a source of T cells could abrogate this increased susceptibility of the BMC to host rejection mechanisms. As determined by histology and 59Fe uptake, the addition of thymocytes resulted in enhanced erythropoiesis. These results suggest that the increased incidence of marrow graft failure when BMC depleted of T cells are used is a result of active rejection by host effector cells and that the adverse effect of marrow T cell depletion can be reversed by the addition of thymocytes.
Murphy
W J
WJ
Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235.
Kumar
V
V
Cope
J C
JC
Bennett
M
M
D000818:Animals; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000276:immunology*; D006084:Graft Rejection; D006410:Hematopoiesis; D006649:Histocompatibility Antigens / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D013601:T-Lymphocytes / Q000276:immunology* / Q000528:radiation effects; D013950:Thymus Gland / Q000166:cytology
D006649:Histocompatibility Antigens