The graft content of donor T cells expressing gamma delta TCR+ and CD4+foxp3+ predicts the risk of acute graft versus host disease after transplantation of allogeneic peripheral blood stem cells from unrelated donors.

TY - JOUR

T1 - The graft content of donor T cells expressing gamma delta TCR+ and CD4+foxp3+ predicts the risk of acute graft versus host disease after transplantation of allogeneic peripheral blood stem cells from unrelated donors.

AU - Pabst, Caroline

AU - Schirutschke, Holger

AU - Ehninger, Gerhard

AU - Bornhäuser, Martin

AU - Platzbecker, Uwe

PY - 2007

Y1 - 2007

N2 - 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(+) T cells in mediating GVHD. Therefore, the aim of this study was to define the yet-unknown role of regulatory and gamma delta TCR(+) 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(6)/kg CD4(+)foxp3(+) and 9.8 x 10(6)/kg gamma delta TCR(+) T cells, respectively. Patients receiving more CD4(+)foxp3(+) 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(+) 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(+) 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.

AB - 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(+) T cells in mediating GVHD. Therefore, the aim of this study was to define the yet-unknown role of regulatory and gamma delta TCR(+) 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(6)/kg CD4(+)foxp3(+) and 9.8 x 10(6)/kg gamma delta TCR(+) T cells, respectively. Patients receiving more CD4(+)foxp3(+) 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(+) 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(+) 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.

M3 - SCORING: Zeitschriftenaufsatz

VL - 13

SP - 2916

EP - 2922

JO - CLIN CANCER RES

JF - CLIN CANCER RES

SN - 1078-0432

IS - 10

M1 - 10

ER -