Selective depletion of major and minor histocompatibility antigen reactiveT cells: towards prevention of acute graft-versus-host disease

Development of acute graft-versus-host disease (aGVHD) following HLA-identi cal sibling bone marrow transplantation (BMT) remains a serious complicatio n. Aselective depletion of T cells has proved to be effective in preventing aGVHD but is associated with relapse and increased incidence of infection. As aGVHD is directed mainly against epithelial tissues we examined whether it would be feasible to selectively deplete T cells reactive with epitheli al cells whilst preserving other specificities. Donor T cells which express HLA-DR, CD25, CD69 and CD71 activation markers after cocultivation with pa tient keratinocytes were depleted using magnetic cell separation techniques . Depletion of major as well as minor histocompatibility antigen activated T cells revealed a significant (P=0.004 and P=0.031, respectively) 10-fold decrease in the frequency of donor T lymphocyte precursors reactive with pa tient keratinocytes. The frequency reactive with third-party and patient pe ripheral blood mononuclear cells, including leukaemia cells, remained uncha nged, supporting the notion that aGVHD and graft-versus-leukaemia (GVL) may be separable. This alloantigen-specific depletion may be used in matched u nrelated as well as HLA-identical sibling BMT for reducing aGVHD whilst con serving GVL.