Abstract
Transplantation tolerance is facilitated by activation-induced apoptosis of peripheral T cells triggered by specific AG: Abs specific for the nonpolymorphic CD3 component of the TCR complex bind to APCs through Fc-FcR interactions, mimic MHC-peptide, and activate polyclonal T cells. In contrast, F(ab')(2) of anti-CD3epsilon Abs do not activate naive T cells but induce apoptosis of Ag-activated, cycling T cells. Here, we report that treatment with anti-CD3epsilon F(ab')(2) can selectively induce apoptosis of donor T cells that recognize a recipient alloantigen, thereby preventing graft-vs-host disease initiated by a TCR-transgenic T cell population. The selective elimination of Ag-activated T cells by non-FcR-binding anti-CD3epsilon Abs could serve as an ideal strategy to prevent graft-vs-host disease and allograft rejection or to treat autoimmune disorders.
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 / metabolism
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Antibodies, Monoclonal / therapeutic use
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Antibody-Dependent Cell Cytotoxicity / genetics
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Apoptosis / genetics
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Apoptosis / immunology
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CD3 Complex*
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Cells, Cultured
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Cytokines / biosynthesis
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Graft vs Host Disease / genetics
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Graft vs Host Disease / pathology
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Graft vs Host Disease / prevention & control*
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Humans
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Immunoglobulin Fab Fragments / metabolism
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Immunoglobulin Fab Fragments / therapeutic use*
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Isoantigens / genetics
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Isoantigens / immunology*
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Isoantigens / metabolism
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Lymphocyte Activation* / genetics
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Lymphocyte Count
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Lymphocyte Depletion*
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Lymphopenia / genetics
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Lymphopenia / pathology
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Lymphopenia / prevention & control
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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, Transgenic
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology*
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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T-Lymphocytes, Cytotoxic / immunology
Substances
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Antibodies, Monoclonal
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CD3 Complex
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CD3E protein, human
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Cytokines
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Immunoglobulin Fab Fragments
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Isoantigens
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Receptors, Antigen, T-Cell