Administration of anti-CD3 antibodies modulates the immune response to an infusion of α-glucosidase in mice.

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.