Induction of oral tolerance in experimental antiphospholipid syndrome by feeding with polyclonal immunoglobulins

Intravenous immunoglobulins (IVIG) contain a wide spectrum of anti-idiotypes associated with autoimmune diseases. Since part of these anti-idiotypes may bear an internal image of the eliciting antigen, IVIG might be suitable for induction of oral tolerance. In the current study we attempted to induce tolerance in an experimental model of anti-phospholipid syndrome (APS) by oral administration of IVIG. Naive mice were fed with IVIG, or anti-β2GPI-specific anti-idiotypic IVIG(αld). Significantly diminished humoral response was noted in mice IVIG/ IVIG-F(ab')₂ or IVIG(αld)-tolerized mice, accompanied by a significant attenuation of clinical manifestations. The maximal effect was achieved in the mice tolerized before disease induction. Abrogation of T lymphocyte proliferation to β2GPI was detected in the mice fed with IVIG prior to β2GPI immunization, mediated by TGFβ and IL-10 secretion. The tolerance induced by IVIG-feeding was nonspecific and could be adoptively transferred to syngeneic mice by CD8α⁺ cells. These CD8α6+ T cells, were found to secrete high levels of TGFβ and IL-10. In summary, IVIG-incluced oral tolerance has a nonspecific immunomodulatory effect in experimental APS, mediated by TGFβ and IL-10-secreting CD8α⁺ cells. Our results point to a possible application of IVIG in the induction of oral tolerance against various autoimmune diseases.