Graft-versus-host disease (GVHD移植物抗宿主病) is a serious risk in many kinds of cell transplants, including for stem cell transplants carried out when stem cells are partially1 depleted2 of conventional T cells, which play an important role in the immune system. Now, researchers at Moffitt Cancer Center have tested a process by which T regulatory cells (Tregs) can be "expanded" to help prevent GVHD. "Tregs play a dominant3 role in transplantation tolerance," said Claudio Anasetti, M.D., corresponding author of a study carried out by a team of Moffitt investigators4 and published in a recent issue of the journal Blood. "Adoptive transfer of freshly isolated5 human Tregs has prevented GVHD in patients treated with allogeneic(同种异体的) (other than self-donated) stem cell transplants. However, some transplants will require a greater number of Tregs that can only be obtained through expanding Tregs outside of the body."
The researchers suggest that therapeutic6 applications will require Tregs to be expanded by more than a hundredfold.
"There is a need to improve on Treg expansion protocols7 before allo-specific Tregs can be brought into the clinic," said Anasetti, chair of the Department of Blood & Marrow8 Transplant at Moffitt.
The authors note that a recently adopted expansion process has used dendritic(树状的) cells to activate9 Tregs.
"Dendritic cells have been identified as having unique capabilities10 for expanding Tregs," cited Anasetti, whose work focuses on preventing GVHD in mouse models and in humans.
To carry out the present study, Anasetti and his fellow researchers adopted a one-step process to expand allo-specific Tregs by dendritic cell stimulation11.
"Our work opens an opportunity to study tissues as sources of antigens for indirect presentation to activate and expand therapeutic Tregs," concluded Anasetti. "If effective, this approach could prevent GVHD while sparing, at least in part, graft-versus-leukemia or graft-versus-tumor responses."