Oral tolerance induction by type V collagen downregulates lung allograft rejection

Immunization with specific proteins or peptides has been used to induce imm unologic tolerance to allografts other than the lung. Recently, we have rep orted that the immune response to lung alloantigen also involves an immune response to type V collagen [col(V)]. The purpose of the current study was to determine if oral administration of col(V) to lung allograft recipients before transplantation downregulates acute rejection episodes. The data sho w that, compared with controls, col(V)-fed recipients had fewer polymorphon uclear cells and lymphocytes in allograft bronchoalveolar lavage fluid, and reduced rejection pathology. Data showing that col(V)fed allograft recipie nts had diminished delayed-type hypersensitivity (DTH) responses to donor a lloantigens suggest that feeding col(V) prevented allograft rejection by in ducing tolerance to donor antigens. Systemic production of transforming gro wth factor (TGF)-beta interleukin (IL)-4, or IL-10 has been reported to be a mechanism for oral tolerance-induced suppression of immune responses. Fee ding col(V) induced upregulated production of TGF-beta but not IL-4 or IL-1 0 in serum. Neutralizing TGF-beta recovered the DTH response to donor antig en in tolerant allograft recipients. Collectively, these data show that ora l administration of col(V) is a novel approach to induce immunologic tolera nce to lung allografts, and that TGF-beta contributed to suppression of the rejection response.