Promotion of fetal liver engraftment by T cells in a murine semiallogeneic model without graft-versus-host reaction.
Graft failure following transplantation with T cell-depleted bone marrow or with tissue naturally devoid of T cells, such as fetal liver (FL), suggests an important role for T cells in ensuring sustained hematopoietic stem cell engraftment. Whether T cells act by eliminating host residual immune cells--or, alternatively, by helping stem cell growth and differentiation--is still to be determined. The purpose of this study was to analyze the effect of T cell supplementation to the FL graft, using a semiallogeneic murine model where the graft-versus-host reaction is absent. Lethally irradiated C3H/OuJ mice were grafted with 10(6) FL cells from (C3H/OuJ x BALB/c) F1 hybrid mice, with or without 10(6) isogeneic mature T cells (FL and FL + T groups). Recipient animals were then monitored for survival and for hematologic and immune reconstitution. Eight days postgrafting, the number of multipotent stem cells in the spleen was significantly higher in FL + T as compared with FL recipient mice. Addition of T cells to the FL graft provided a faster recovery of hematological parameters and a significant increase in short-term survival (25.5% 6 weeks of survival in the FL group, as opposed to 55.5% 6 weeks of survival in the FL + T group, P less than 0.01). By contrast, immunological functions, as assessed by mitogen responses, were quite similar in both groups of animals. Overall a promoting effect of T cells in early stem cell engraftment was clearly demonstrated in this murine model, where GVHR is absent. These results provide in vivo support for a direct T cell effect on hematopoiesis.
Navarro
J
J
Unité de Recherches en Néphro-Urologie, Transplantation, et Immunologie Clinique, INSERM U80, CNRS UA 1177, Université Claude Bernard, Lyon, France.
Touraine
J L
JL
D000818:Animals; D001772:Blood Cell Count; D016026:Bone Marrow Transplantation; D002678:Chimera; D006087:Graft vs Host Reaction; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D016031:Liver Transplantation; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D013601:T-Lymphocytes / Q000502:physiology*