Prevention of bronchiolitis obliterans in rat lung allografts by type V collagen-induced oral tolerance

Background. We have reported that feeding type V collagen (col(V)) to lung allograft recipients induce immune tolerance that prevents acute lung allograft rejection. Repeated acute rejection is a risk factor for or associated with chronic rejection, known as bronchiolitis obliterans (BO), the leading cause of death in lung allograft recipients. The current study examine if col(V)-induced oral tolerance prevents BO. Methods. WKY rats (RT1(1)) were fed either col(V) or diluent before orthotopic transplantation of F344 (RT1(1v1)) lung allografts. No rats received any immuno suppression. At 10 weeks posttransplantation the time to onset of BO, delayed type hypersensitivity (DTH responses to donor antigens, and col(V) were examined. In addition, proliferative responses of recipient T lymphocytes to donor antigens, and ability of recip ient antigen presenting cells to present alloantigens in lung allografts were evaluated. Results. The data show that recipient rats have sus tained DTH responses to donor antigens and col(V). T lymphocytes from col(V)-fed lung allograft recipient were unable to proliferate in response to donor antigens, but feeding col(V) had no effect on the presentation of donor alloantigens by recipient antigen pre senting cells. All diluent fed rats developed BO, but only mild acute rejection (grade 2) was present in all rats fed col(V). Transforming growth factor (TGF)-beta-production was up-regulated systemically in col(V) fed, but not diluent fed, lung allograft recipients, and neutralizing TGF-36 recovered the DTH response to donor antigens in col(V)-fed rats. Conclusions. Collectively these data show that col(V)-induces oral tolerance that prevents BO, and that tolerance may be mediated by systemic production of TGF-36.