Persistence of donor-reactive CD4⁺ T cells in liver and spleen of rats tolerant to a liver allograft

Background. In the rat, orthotopic liver transplantation from a DA strain donor to a PVG recipient causes an early rejection response that spontaneously resolves over the following weeks to yield long-lasting, donor- specific tolerance. Methods. Limiting dilution analysis was used to estimate the frequencies of host CD4⁺ cells able to proliferate in response to donor antigens in the grafted liver and spleen of recipients during and after tolerance induction. Results. Compared with naive PVG rats, both the frequencies and absolute numbers of donor-reactive host CD4⁺ cells in the liver and spleen rose significantly during the first week after transplantation and remained elevated for at least 3 months. Conclusion. We conclude that the development of tolerance in this model is not associated with deletion of clonogenic donor-reactive CD4⁺ T cells by clonal exhaustion or any other mechanism.