Division rate and phenotypic differences discriminate alloreactive and nonalloreactive T cells transferred in lethally irradiated mice

After non-T-cell-depleted allogeneic hematopoietic stem cell transplantatio n (HSCT), both alloreactive and homeostatic signals drive proliferation of donor T cells. Host-reactive donor T cells, which proliferate on alloantige n stimulation, are responsible for the life-threatening graft-versus-host d isease. Non-host-reactive donor T cells, which proliferate in response to h omeostatic signals, contribute to the beneficial peripheral T-cell reconsti tution. The elimination of alloreactive T cells is a major therapeutic chal lenge for HSCT and would greatly benefit from their specific identification . After T-cell transfer in lymphopenic recipients, the present results show that alloreactive T cells rapidly divided; up-regulated CD69, CD25, and CD 4 molecules; and down-regulated CD62L. In contrast, nonalloreactive T cells started to divide later and did not up-regulate CD69, CD25, and CD4. Thus, these 2 cell populations can be effectively discriminated. This should fac ilitate the specific depletion of alloreactive T cells in allogeneic HSCT. (C) 2001 by The American Society of Hematology.