Celiac.com 09/15/2009 - Active delivery of recombinant autoantigens or allergens to intestinal mucosa by genetically modified Lactococcus lactis (LL) offers a unique therapeutic approach for the induction of tolerance to gluten proteins.
A team of researchers recently set out to determine whether oral administration of LL-delivered DQ8-specific gliadin epitope induces Ag-specific tolerance.
Celiac disease is associated with either HLA-DQ2- or HLA-DQ8-restricted responses to specific antigenic epitopes of gliadin, and may be treated by induction of Ag-specific tolerance.
The research team engineered LL to secrete a deamidated DQ8 gliadin epitope (LL-eDQ8d) and then observed the induction of Ag-specific tolerance in NOD AB degrees DQ8 transgenic mice. The team measured tolerance by delayed-type hypersensitivity reaction, cytokine measurements, eDQ8d-specific proliferation, and regulatory T cell analysis.
Oral administration of LL-eDQ8d induced suppression of local and systemic DQ8-restricted T cell responses in NOD AB degrees DQ8 transgenic mice. Result was an Ag-specific decrease of the proliferative capacity of inguinal lymph node (ILN) cells and lamina propria cells. Production of IL-10 and TGF-beta and a significant induction of Foxp3(+) regulatory T cells were associated with the eDQ8d-specific suppression induced by LL-eDQ8d.
These results support the development of orally administered Ag-secreting LL to treat gluten-sensitive disorders. Such treatments may be effective even in cases of established hypersensitivity.