922 TREATMENT OF MURINE AND HUMAN BONE MARROW WITH MONO-CLONAL ANTIBODIES TO T LYMPHOCYTES TO PREVENT GRAFT VERSUS HOST DISEASE (GVHD)

Abstract

GVHD is the major limitation to human allogeneic bone marrow transplantation (BMT). A murine model of BMT was developed to study acute and chronic GVHD due to non-major histocompatibility region (MHR) antigens. Lethally irradiated C57B1/6 mice were transplanted with bone marrow and spleen cells from LP mice. When recipients were transplanted with 1-10 × 106 spleen cells in addition to 10 × 106 bone marrow cells, 31 of 91 animals developed acute GVHD, 19 chronic GVHD, and 41 no GVHD. The in vitro removal of mature T lymphocytes by treatment with a monoclonal antibody to murine T lymphocytes and complement eliminated GVHD in all of 50 recipients. Recipient mice developed normal hematocrits, adult hemoglobin electrophoretic patterns, and normal T cell function by three months. Human bone marrow cells treated with a monoclonal antibody to mature T lymphocytes (OKT-3) and complement had no residual detectable T cells as determined by E-rosette formation (16% pretreatment; 0%, post-treatment) or by indirect immunofluorescence(17% pre; 0% post). The total number of nucleated cells was reduced by 50% during treatment with no decrease in the frequency of hematopoietic precursors (BFU-E colonies). The use of monoclonal antibodies to remove mature T lymphocytes from human bone marrow may be an effective method to prevent human GVHD.