Anti-CD3 epsilon F(ab')2 prevents graft-versus-host disease by selectively depleting donor T cells activated by recipient alloantigens.
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.
Yu
X Z
XZ
Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Bidwell
S J
SJ
Martin
P J
PJ
Anasetti
C
C
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000627:therapeutic use; D000920:Antibody-Dependent Cell Cytotoxicity / Q000235:genetics; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D017252:CD3 Complex; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D006086:Graft vs Host Disease / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism / Q000627:therapeutic use*; D007519:Isoantigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008231:Lymphopenia / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; C115335:CD3E protein, human; D016207:Cytokines; D007140:Immunoglobulin Fab Fragments; D007519:Isoantigens; D011948:Receptors, Antigen, T-Cell