Anti-CD3 epsilon F(ab')2 prevents graft-versus-host disease by selectively depleting donor T cells activated by recipient alloantigens

J Immunol. 2001 May 1;166(9):5835-9. doi: 10.4049/jimmunol.166.9.5835.

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

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Monoclonal / therapeutic use
  • Antibody-Dependent Cell Cytotoxicity / genetics
  • Apoptosis / genetics
  • Apoptosis / immunology
  • CD3 Complex*
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Graft vs Host Disease / genetics
  • Graft vs Host Disease / pathology
  • Graft vs Host Disease / prevention & control*
  • Humans
  • Immunoglobulin Fab Fragments / metabolism
  • Immunoglobulin Fab Fragments / therapeutic use*
  • Isoantigens / genetics
  • Isoantigens / immunology*
  • Isoantigens / metabolism
  • Lymphocyte Activation* / genetics
  • Lymphocyte Count
  • Lymphocyte Depletion*
  • Lymphopenia / genetics
  • Lymphopenia / pathology
  • Lymphopenia / prevention & control
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Antibodies, Monoclonal
  • CD3 Complex
  • CD3E protein, human
  • Cytokines
  • Immunoglobulin Fab Fragments
  • Isoantigens
  • Receptors, Antigen, T-Cell