The repopulation capacity of bone marrow grafts following pretreatment with monoclonal antibodies against T lymphocytes in rhesus monkeys

Abstract

Complement-mediated lysis of (subsets of) T lymphocytes in bone marrow grafts is increasingly used to prevent acute graft-versus-host disease in human bone marrow transplant recipients, especially in case of major immunogenetic disparity between donor and recipient. Since T lymphocyte depletion has resulted in an increased frequency of allogeneic engraftment failures, its effect on hemopoietic reconstitution was measured in rhesus monkeys. The reactivity patterns of commonly used types of antihuman T lymphocyte monoclonal antibodies (MCAs) with rhesus monkey lymphocytes was analyzed using a double-label cytofluorometry technique and found to be very similar to those with human lymphocytes. The antibodies investigated included CAMPATH-1 (recognizing an antigen present on virtually all lymphocytes and monocytes), OKT4 + 4a (CD4, helper/inducer T lymphocytes), B9 (CD8, suppressor/cytotoxic T lymphocytes), WT-1 (CD7, pan-T), and anti-DR MCAs as stem cell toxic controls. Their possible toxicity to hemopoietic stem cells was studied by using a semiquantitative autologous regeneration assay. Cytotoxic lysis of cells in the bone marrow grafts reacting with the T lymphocyte purging MCAs did not result in delayed regeneration compared to untreated autologous grafts. It is concluded that T lymphocyte depletion using anti-T-lymphocyte MCAs does not influence the repopulating capacity of an autologous bone marrow graft.