title: Administration of anti-CD3 antibodies modulates the immune response to an infusion of α-glucosidase in mice.
abstract: Animal and human studies of enzyme replacement therapy (ERT) for Pompe disease (PD) have indicated that antibodies (Abs) generated against infused recombinant human α-glucosidase (rhGAA) can have a negative impact on the therapeutic outcome and cause hypersensitivity reactions. We showed that parenteral administration of anti-CD3 Abs into mice can reduce the titer of anti-human GAA Abs in wild-type mice administered the enzyme. Mice that had been treated with anti-CD3 Abs and then subjected to a secondary challenge with rhGAA showed a lower increase in Ab titers than control mice. Moreover, the administration of anti-CD3 Abs also reduced the levels of pre-existing Abs. Treatment with anti-CD3 Abs also prevented a lethal hypersensitivity reaction and reduced the Ab titers in a mouse model of PD. Mice treated with anti-CD3 Abs showed reduced numbers of CD4(+) and CD8(+) cells, and an increased ratio of CD4(+)CD25(+)/CD4(+) and CD4(+)CD25(+)FoxP3(+)/CD4(+) cells. When the CD4(+)CD25(+) cells were depleted using anti-CD25 Abs, the observed reduction in Abs against the enzyme by anti-CD3 Abs was abrogated. This suggests that CD4(+)CD25(+) cells are important for the immune suppressive activity of anti-CD3 Abs. In summary, anti- CD3 Abs are useful for inducing immune tolerance to ERT for PD.
authors.affiliation: Department of Gene Therapy, Institute of DNA Medicine, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan. tohashi@jikei.ac.jp
authors.forename: Toya
authors.initials: T
authors.lastname: Ohashi
authors.forename: Sayoko
authors.initials: S
authors.lastname: Iizuka
authors.forename: Yohta
authors.initials: Y
authors.lastname: Shimada
authors.forename: Takashi
authors.initials: T
authors.lastname: Higuchi
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Eto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D017252:CD3 Complex / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D056947:Enzyme Replacement Therapy; D006009:Glycogen Storage Disease Type II / Q000628:therapy*; D007108:Immune Tolerance / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000627:therapeutic use; D000520:alpha-Glucosidases / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D011994:Recombinant Proteins; D000520:alpha-Glucosidases