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

• Published in: Clinical cancer research 2007-05, Vol.13 (10), p.2916-2922
• Main Authors: Pabst, Caroline, Schirutschke, Holger, Ehninger, Gerhard, Bornhäuser, Martin, Platzbecker, Uwe
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; CD4 Antigens - analysis; Female; Forkhead Transcription Factors - analysis; Graft vs Host Disease - diagnosis; Graft vs Host Disease - epidemiology; Graft vs Host Disease - mortality; Humans; Incidence; Male; Middle Aged; Peripheral Blood Stem Cell Transplantation; Prognosis; Receptors, Antigen, T-Cell, gamma-delta - analysis; Recurrence; Risk; T-Lymphocytes - chemistry; T-Lymphocytes - immunology; T-Lymphocytes, Regulatory - chemistry; T-Lymphocytes, Regulatory - immunology; Tissue Donors
• ISSN: 1078-0432
• DOI: 10.1158/1078-0432.CCR-06-2602

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. 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. 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. 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.