Regulatory cells develop after the spontaneous acceptance of rat liver allografts

Background. After donor-specific transfusion, tolerance to heart transplants is serially passed to naive rats by the adoptive transfer of long term survivor (LTS)-tolerant splenocytes (SC). We examined whether regulatory cells similarly develop after the spontaneously accepted Lewis. (LEW) to Dark Agouti (DA) liver transplants. Methods. SC from a LTS DA rat with a LEW liver were adoptively transferred to a naive DA 1 day before transplantation of an irradiated (1000 rad) LEW liver. Results. Untreated LEW to DA liver allografts were uniformly accepted; whereas all irradiated LEW liver grafts were rejected. In contrast, when 1.5 X 10(8) DA LTS SC were transferred to a naive DA recipient, all irradiated LEW liver grafts were accepted. When decreased to 1.0 X 10(8) LTS DA SC, only 1 of 4 irradiated LEW grafts was accepted. However, if 1.5 X 10(8) DA SC harvested only 30 days after liver transplantation were transferred, only 2 of 5 irradiated LEW liver grafts were accepted. The serial second and third adoptive transfers of 1.5 X 10(8) DA LTS SC also resulted in the uniform acceptance of irradiated LEW livers. Conclusion. Regulatory cells that develop after the spontaneous acceptance of a LEW to DA liver transplant can serially transfer tolerance to new naive LEW liver allograft DA recipients. This "infectious tolerance" is dependent on the time of cell harvest after transplantation and on the cell dose given.