Abstract
A major goal of the transplant field is to tolerize donor T cells to prevent graft-versus-host disease (GVHD) (1). We describe an ex vivo approach in which the blockade of CD40 ligand (CD40L:CD154):CD40 interactions, a pathway required for optimal T cell expansion, induces donor CD4(+) T cells to become tolerant to host alloantigens (2). High doses of tolerized cells did not cause GVHD lethality in vivo. T cells had intact responses to antigens not present during tolerization. Tolerance was long lived and not readily reversible in vivo. These data have significant implications for the use of tolerization approaches to prevent human GVHD.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / pharmacology
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Antibodies, Monoclonal / therapeutic use*
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / transplantation
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CD40 Antigens / immunology*
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CD40 Ligand
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Cells, Cultured
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Graft vs Host Disease / immunology
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Graft vs Host Disease / prevention & control*
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Immunosuppression Therapy*
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Interleukin-2 / pharmacology
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Isoantigens / immunology*
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Lymphocyte Culture Test, Mixed
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Membrane Glycoproteins / antagonists & inhibitors
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Membrane Glycoproteins / immunology*
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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, SCID
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Specific Pathogen-Free Organisms
Substances
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Antibodies, Monoclonal
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CD40 Antigens
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Interleukin-2
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Isoantigens
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Membrane Glycoproteins
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CD40 Ligand