Donor Regulatory T Cells Identified by FoxP3 Expression but Also by the Membranous CD4+CD127low/neg Phenotype Influence Graft-versus-tumor Effect After Donor Lymphocyte Infusion

Regulatory T cells (T-reg) play a pivotal role in the control of graft-versus-host disease (GVHD) and might also influence the graft-versus-tumor effect after allogeneic stem cell transplantation. We assessed this role after donor lymphocyte infusions (DLIs) by quantifying T-reg in DLI products, using the CD25, Foxp3 but also the recently identified CD127 T-reg markers. Compared with others, patients in durable complete remission of their malignancy after DLI had received a lower number of FoxP3(+)CD25(+), FoxP3(+) CD127(low/neg), or CD4(+)CD127(low/neg) T-reg cells (P = 0.04). The CD4(+)CD127(low/neg) Treg content of DLI remained significantly correlated with the hematologic response in multivariate analysis (P = 0.05). T-reg may thus inhibit graft-versus-tumor effect after DLI, a setting where the antitumoral effect observed is only driven by T-cell-mediated cytotoxicity, independently of any other associated treatment. In comparison with the intracytoplasmic Foxp3 marker, the membranous CD4(+) CD127(low/neg) phenotype of T-reg could be particularly relevant to manipulate this cell population, to increase the antitumoral response in strategies of allogeneic or autologous immunotherapy.