FAILURE OF AUTOLOGOUS MARROW RECONSTITUTION AFTER CYTOLYTIC TREATMENT OF MARROW WITH ANTI-IA MONOCLONAL-ANTIBODY

  • 1 January 1985
    • journal article
    • research article
    • Vol. 65  (4) , 819-822
Abstract
Hematopoietic stem cell toxicity of the murine monoclonal antibody 7.2, recognizing la-like antigens on canine cells, was tested in an autologous bone marrow transplantation model. Dogs were given 9.2 Gy [gray] of total body irradiation followed by the infusion of autologous marrow treated by 1 of 2 methods to remove la+ cells. In 6 dogs, the marrow cells were pelleted, treated with antibody 7.2 (1:1,000) and rabbit complement (1:4), resuspended in culture medium, and infused. All 6 dogs had prompt and sustained engraftment surviving > 26 days. Indirect immunofluorescence showed that the depletion of Ia+ cells was incomplete. Four dogs received marrow cells first separated by density gradient centrifugation and then treated with an excess of antibody 7.2 and 2 cycles of undiluted rabbit complement. None of these dogs, surviving 17-22 days, had sustained engraftment. With antibody 7.2 used as the marker, only 1 dog had detectable residual la+ cells (0.9%) after treatment. Dogs receiving marrow cells obtained by density gradient centrifugation without additional manipulation, or with subsequent treatment with complement only or with complement and an antibody (DT-2) directed at a subpopulation of T cells, engrafted promptly and completely. la+ bone marrow cells are essential for the successful engraftment of transplanted marrow in dogs.