Amc. Van Dijk et al., Selective depletion of major and minor histocompatibility antigen reactiveT cells: towards prevention of acute graft-versus-host disease, BR J HAEM, 107(1), 1999, pp. 169-175
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.