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Antiviral immunity and T-regulatory cell function are retained after selective alloreactive T-cell depletion in both the HLA-identical and HLA-mismatched settings

Davies, JK; Koh, MBC; Lowdell, MW; (2004) Antiviral immunity and T-regulatory cell function are retained after selective alloreactive T-cell depletion in both the HLA-identical and HLA-mismatched settings. BIOL BLOOD MARROW TR , 10 (4) 259 - 268. 10.1016/j.bbmt.2003.12.001.

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Abstract

Nonselective T-cell depletion reduces the incidence of severe graft-versus-host disease after allogeneic hematopoietic stem cell transplantation, but the cost is delayed and disordered antigen-specific immune reconstitution and increased infection. We use a method of selective depletion of alloreactive T cells expressing the activation marker CD69 after coculture with stimulator cells in a modified or standard mixed lymphocyte reaction. The technique has been shown to reduce alloreactivity while retaining third-party responses in vitro and, in a mismatched murine model, led to donor T-cell engraftment with a virtual absence of graft-versus-host disease and increased survival. We show in a human HLA-mismatched and unrelated HLA-identical setting that this technique retains > 80% of specific cellular antiviral activity by cytomegalovirus-tetramer analysis and cytomegalovirus/Epstein-Barr virus peptide-stimulated interferon-gamma ELISpot assay. Furthermore, CD4(+) CD25(+) T-regulatory cells are not removed by this method of selective allodepletion and retain their function in suppressing allogeneic proliferative responses. Preservation of antiviral cytotoxic T lymphocytes in selectively allodepleted stem cell grafts would lead to improved antiviral immunity after transplantation. The retention of immunosuppressive CD4(+) CD25(+) T-regulatory cells could lead to more ordered immune reconstitution and further suppress alloreactive responses after transplantation. (C) 2004 American Society for Blood and Marrow Transplantation.

Type: Article
Title: Antiviral immunity and T-regulatory cell function are retained after selective alloreactive T-cell depletion in both the HLA-identical and HLA-mismatched settings
DOI: 10.1016/j.bbmt.2003.12.001
Keywords: depletion, graft-versus-host disease, allogeneic hematopoictic stem cell transplantation T-regulatory cells, GRAFT-VERSUS-HOST, BONE-MARROW-TRANSPLANTATION, MINOR HISTOCOMPATIBILITY ANTIGEN, RESPIRATORY SYNCYTIAL VIRUS, CYTOMEGALOVIRUS-INFECTION, DISEASE PROPHYLAXIS, GVHD PROPHYLAXIS, LEUKEMIA, LYMPHOCYTES, IMMUNOTOXIN
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/6942
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