Evidence that reduction of immunogenicity of T-depleted bone marrow depends on additional depletion of accessory cells. Implications for prevention of graft rejection.
An effective prophylaxis of graft-versus-host reaction in clinical bone marrow transplantation can be achieved by T depletion of the graft. However, this kind of graft manipulation is accompanied by a strongly increased incidence of graft rejection. In order to eliminate this hazardous complication we studied the possibility of preventing rejection of a BM graft by reducing its immunogenicity. In this report we demonstrate that the capacity of human BM cells to induce proliferation of allogeneic T cells is strongly reduced after treatment with the antilymphocyte/antimonocyte monoclonal antibody K31+ rabbit complement (C), indicating a reduced immunogenicity of the BM cells. On the other hand, the allostimulatory capacity of BM treated with clinically established T-depleting MoAbs, including the more broadly reactive CAMPATH-1, was not or only slightly reduced. MHC class II induction on BM cells with human recombinant gamma-interferon did not restore the allostimulatory capacity reduced by K31+C. Exogenous IL-1 partially inhibited the K31-mediated reduction of allostimulatory capacity. Reduction of the allostimulatory capacity of BM cells with K31+C correlated with a reduction of their capacity to support mitogen-induced proliferation of purified autologous T cells, indicating the absence of accessory functions. Addition of autologous peripheral adherent cells to K31+C treated BM restored its accessory function as well as its allostimulatory capacity. Labeling studies confirmed that accessory cells are critical for the described K31-mediated effects. We conclude that depletion of accessory cells in addition to lymphocytes with K31+C strongly reduces the immunogenicity of a BM graft, may help prevent graft rejection, and may serve as a model for preconditioning other organ grafts.
Dreger
P
P
Department of Immunology, University of Kiel, West Germany.
Müller-Ruchholtz
W
W
D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology*; D001854:Bone Marrow Cells; D002469:Cell Separation; D005434:Flow Cytometry; D006084:Graft Rejection; D006801:Humans; D007165:Immunosuppression Therapy; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007375:Interleukin-1; D011994:Recombinant Proteins; D007371:Interferon-gamma