Negative depletion of CD3(+) and TcRαβ(+) T cells

In contrast to CD34(+) positive selection, negative depletion strategies retain large numbers of effector cells in allogeneic peripheral stem cell grafts, such as natural killer (NK) and other cells. This review summarizes the clinical experience obtained using negative depletion approaches of CD3(+) and T-cell receptor (TcR)αβ(+) T lymphocytes.

Attempts to improve immune reconstitution and to better exploit the graft-versus-malignancy effect after transplantation of T-cell-depleted grafts through the preservation of immune effector cells led to the development of CD3-, CD3/CD19- and more recently TcRαβ/CD19-negative depletion strategies of mobilized peripheral stem cell grafts. A faster immune reconstitution has been observed in patients with negatively depleted grafts after haploidentical transplantation, although no prospective randomized trials have been reported to date. In a randomized study of matched sibling and matched unrelated transplantation, CD3/CD19-depleted peripheral stem cell grafts led to a faster recovery of NK cells compared with the CD34(+)-positive selection group.

New technologies allow the large-scale graft engineering of peripheral stem cells for clinical use in matched and mismatched stem cell transplantation. Further clinical trials are necessary to decide which of these methods is associated with a faster immune reconstitution and a better outcome after transplantation.