Bone marrow transplantation with T lymphocyte depleted and stem cell enriched bone marrows grafts : experiments in Rhesus monkeys

The major complication after allogeneic bone marrow transplantation is the occurrence of acute GvHD. This complication can be successfully prevented when T lymphocytes are depleted from a bone marrow graft. The beneficial effect of prevention of acute GvHD is counterbalanced by an increased frequency of engraftment failures. In view of this problem several experiments were planned to unravel whether the engraftment failures after T lymphocyte depletion were attributable to the loss of the trophic function of T lymphocytes or were attributable to the loss of the immunosuppressive action of donor Tlymphocytes. When the latter option is valid, more immunosuppression of the recipient would result in sustained engraftment ofT lymphocyte depleted bone marrow grafts. With regard to T lymphocyte depletion, it was attempted to positively select for stem cells and concomitantly negatively select for T lymphocytes. Stem cells are the essential cells in a bone marrow graft since they are responsible for sustained engraftment. A positive selection of these cells would yield an uniform method for preparation of a bone marrow graft rich in stem cells and fully depleted of T lymphocytes. A second approach was to investigate whether depletion of a subpopulation of T lymphocytes (helper/inducer or suppressor/ cytotoxic T lymphocytes) was sufficient to prevent acute GvHD.

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