Loss of proliferative capacity and T cell immune development potential by bone marrow from mice undergoing a graft-vs-host reaction

Abstract

The inoculation of parental T lymphocytes into healthy, immune-competent F1 hybrid mice can result in severe immunologic abnormalities including immune deficiency in the recipients. To test whether stem cell function could also be affected in F1 mice undergoing a parental-induced graft-vs-host (GVH) reaction, T cell-depleted bone marrow from parentally injected F1 mice was tested for stem cell proliferative capacity and for differentiation into functional T cells by transplantation of bone marrow from GVH mice into lethally irradiated, syngeneic F1 test recipients. Stem cell proliferative capacity was assessed in the repopulating spleens of the test mice by the in vivo [125I]Iodo-2'-deoxyuridine assay. An eightfold to 10-fold reduction could be observed in the proliferative capacity of marrow from mice in which a GVH reaction had been induced 6 wk earlier. The GVH-induced hematopoietic defect required parental T cell recognition of both class I and class II H-2 alloantigens expressed by the F1 host. No suppressor cell activity was detected in the marrow of GVH mice. We did not detect a defect in the microenvironment of mice injected with parental marrow, but we did observe a severe and long-lasting defect in the ability of GVH F1 recipients to support the growth of F1 bone marrow. Spleen cells of test recipients repopulated with marrow from GVH donors exhibit in vitro defects in T and B lymphocyte functions. These findings indicate that the GVH reaction can affect early stages in the development of the hematopoietic system, both in terms of stem cell proliferative capacity and of long-term T lymphocyte functional potential.