Editors' ChoiceImmunology

Donor monocytes suppress graft-versus-host disease

Science Signaling  07 Apr 2015:
Vol. 8, Issue 371, pp. ec87
DOI: 10.1126/scisignal.aab2803

When the donor cannot be matched to a patient with bone marrow dysfunction, the donor hematopoietic stem cells may attack the host in a process called graft-versus-host disease (GVHD). D’Aveni et al. show that when human donors were administered granulocyte colony-stimulating factor (G-CSF) prior to collection of peripheral blood stem cells (referred to as G-CSF-mobilized stem cells), the collected cells included a previously uncharacterized population of immunosuppressive CD34+ cells that had characteristics similar to mature monocytes. In coculture experiments with these cells isolated from G-CSF-mobilized stem cells from humans or mice, the CD34+ monocytes inhibited the proliferation of activated T cells. Further experiments with the mouse CD34+ monocytes revealed that the inhibitory effect on T cells depended on interferon-γ produced by the T cells, cell-cell contact, and production of nitric oxide (NO) by the CD34+ monocytes and not only prevented proliferation but induced apoptosis of the activated T cells. In a mouse model of GVHD, coadministration of CD34+ monocytes with the donor cells resulted in fewer activated donor T cells and more donor-derived regulatory T cells, consistent with their immunosuppressive activity. Because fraction of these CD34+ monocytes in peripheral blood inversely correlated with GVHD in patients, expanding these cells before transplant may decrease the risk of GVHD.

M. D’Aveni, J. Rossignol, T. Coman, S. Sivakumaran, S. Henderson, T. Manzo, P. Santos e Sousa, J. Bruneau, G. Fouquet, F. Zavala, O. Alegria-Prévot, M. Garfa-Traoré, F. Suarez, H. Trebeden-Nègre, M. Mohty, C. L. Bennett, R. Chakraverty, O. Hermine, M.-T. Rubio, G-CSF mobilizes CD34+ regulatory monocytes that inhibit graft-versus-host disease. Sci. Transl. Med. 7, 281ra42 (2015). [Abstract]