Lethal graft-versus-host disease after bone marrow transplantation across minor histocompatibility barriers in mice. Prevention by removing mature T cells from marrow.

Abstract

In two situations, transfer of normal unsensitized bone marrow cells into heavily irradiated H-2-identical allogeneic mice caused a high incidence of lethal chronic graft-versus-host disease (GVHD), i.e. mortality occuring between days of 20 and 80 postirradiation. Minor histocompatibility determinants appeared to be the main target for eliciting GVHD. Removing mature T cells from the marrow with anti-Thy 1.2 serum and complement before injection prevented GVHD. On the basis of adding purified T cells to T-cell-depleted marrow cells, it was concluded that contamination of the marrow with as few as 0.3% T cells was sufficient to cause a high incidence of lethal GVHD in certain situations. No GVHD was found with the injection of non-T cells (Thy 1.2-negative cells) or with tolerant T cells. Irradiated recipients of T-cell-depleted marrow cells remained in good health for prolonged periods. These mice showed extensive chimerism with respect to the donor marrow, normal numbers of T and B cells and were immunocompetent. The data provide no support for the view that chronic GVHD developing after bone marrow transplantation in man is the result of an attack by the progeny of the donor stem cells. The results imply that mature T cells contaminating marrow inocula are probably the main cause of GVHD seen in the clinical situation.