The Graft Content of Donor T Cells Expressing gamma delta TCR super(+) and CD4 super(+)foxp3 super(+) Predicts the Risk of Acute Graft versus Host Disease after Transplantation of Allogeneic Peripheral Blood Stem Cells from Unrelated Donors

PURPOSE: Recently, high numbers of regulatory T cells within the stem cell graft were described to be associated with less graft-versus-host disease (GVHD) after related peripheral blood stem cell transplantation (PBSCT). Studies in mice also suggest a distinct role of gamma delta TCR super(+) T cells in mediating GVHD. Therefore, the aim of this study was to define the yet-unknown role of regulatory and gamma delta TCR super(+) T cells in human PBSCT from unrelated donors. Experimental Design: The frequency of both T-cell subsets within the graft was analyzed in 63 patients receiving unrelated allogeneic PBSCT. The respective amounts were quantified by flow cytometry and PCR and further correlated with clinical outcome. RESULTS: The grafts contained a median of 11.2 x 10 super(6)/kg CD4 super(+)foxp3 super(+) and 9.8 x 10 super(6)/kg gamma delta TCR super(+) T cells, respectively. Patients receiving more CD4 super(+)foxp3 super(+) cells had a lower cumulative incidence of acute GVHD II-IV (44% versus 65%, P = 0.03). Interestingly, in patients who received higher concentrations of donor gamma delta TCR super(+) T cells, acute GVHD II-IV was more frequent (66% versus 40%, P = 0.02). In multivariate analysis, only the graft concentration of gamma delta TCR super(+) T cells (P = 0.002) and a positive cytomegalovirus status of the recipient (P = 0.03) were significantly associated with the occurrence of acute GVHD II-IV. CONCLUSION: Graft composition of T-cell subsets seems to affect the outcome of patients receiving allogeneic PBSCT from unrelated donors. Therefore, selective manipulation or add-back of particular subsets might be a promising strategy to reduce the incidence of GVHD.