Abstract
Mature donor T cells cause graft-versus-host disease (GVHD), but they are also the main mediators of the beneficial graft-versus-tumor (GVT) activity of allogeneic bone marrow transplantation. Suppression of GVHD with maintenance of GVT activity is a desirable outcome for clinical transplantation. We have previously shown that donor-derived CD4+CD25+ regulatory T cells inhibit lethal GVHD after allogeneic bone marrow transplantation across major histocompatibility complex (MHC) class I and II barriers in mice. Here we demonstrate that in host mice with leukemia and lymphoma, CD4+CD25+ regulatory T cells suppress the early expansion of alloreactive donor T cells, their interleukin-2-receptor (IL-2R) alpha-chain expression and their capacity to induce GVHD without abrogating their GVT effector function, mediated primarily by the perforin lysis pathway. Thus, CD4+CD25+ T cells are potent regulatory cells that can separate GVHD from GVT activity mediated by conventional donor T cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Bone Marrow Transplantation / adverse effects
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Bone Marrow Transplantation / immunology*
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Bone Marrow Transplantation / methods
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / immunology
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Cell Survival
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Female
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Graft vs Host Disease / immunology
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Graft vs Host Disease / prevention & control*
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Interferon-gamma / metabolism
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Interleukin-2 Receptor alpha Subunit
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Leukemia / immunology
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Leukemia / pathology
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Leukemia / therapy
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Lymphoma / therapy
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Mutant Strains
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Perforin
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Pore Forming Cytotoxic Proteins
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Receptors, Interleukin / metabolism
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Receptors, Interleukin-2 / metabolism
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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Transplantation, Homologous / adverse effects
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Transplantation, Homologous / immunology
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Transplantation, Homologous / methods
Substances
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Il2ra protein, mouse
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Interleukin-2 Receptor alpha Subunit
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Membrane Glycoproteins
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Pore Forming Cytotoxic Proteins
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Receptors, Interleukin
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Receptors, Interleukin-2
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Perforin
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Interferon-gamma