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

Authors' Affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum "Carl Gustav Carus" Dresden, Dresden, Germany

Requests for reprints: Uwe Platzbecker, Medizinische Klinik und Poliklinik I, Universitätsklinikum "Carl Gustav Carus" Dresden, 01307 Dresden, Germany. Phone: 49-351-458-4190; Fax: 49-351-458-5362; E-mail: Uwe.Platzbecker{at}uniklinikum-dresden.de.

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 TCR⁺ T cells in mediating GVHD. Therefore, the aim of this study was to define the yet-unknown role of regulatory and 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 10⁶/kg CD4⁺foxp3⁺ and 9.8 x 10⁶/kg 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 TCR⁺ T cells, acute GVHD II-IV was more frequent (66% versus 40%, P = 0.02). In multivariate analysis, only the graft concentration of 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.