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 | Toya Ohashi, Sayoko Iizuka, Yohta Shimada, Takashi Higuchi, Yoshikatsu Eto, Hiroyuki Ida, Hiroshi Kobayashi |
Journal | Molecular therapy : the journal of the American Society of Gene Therapy
(Mol Ther)
Vol. 20
Issue 10
Pg. 1924-31
(Oct 2012)
ISSN: 1525-0024 [Electronic] United States |
PMID | 22871665
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antibodies, Monoclonal
- CD3 Complex
- Recombinant Proteins
- alpha-Glucosidases
|
Topics |
- Animals
- Antibodies, Monoclonal
(immunology, therapeutic use)
- CD3 Complex
(immunology)
- CD4-Positive T-Lymphocytes
(immunology)
- Disease Models, Animal
- Enzyme Replacement Therapy
- Glycogen Storage Disease Type II
(therapy)
- Immune Tolerance
(immunology)
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Mice, Knockout
- Recombinant Proteins
(therapeutic use)
- alpha-Glucosidases
(therapeutic use)
|