Use of Allograft Biopsies to Assess Thymopoiesis after Thymus Transplantation

Abstract

Thymus allograft biopsies were performed in athymic infants with complete DiGeorge anomaly after thymus transplantation to assess whether the thymus allograft tissue was able to support thymopoiesis. Forty-four consecutive infants were treated with postnatal cultured thymus allografts. Thirty biopsies and six autopsies evaluating the allograft site were obtained in 33 infants, 23 of whom survive. The allograft was examined by immunohistochemistry for evidence of thymopoiesis. Grafted thymus tissue was found in 25 of 30 biopsies, 23 of which showed thymopoiesis. All 19 survivors with thymopoiesis on biopsy developed naive T cells and T cell function. Autopsies were done in six subjects, three of whom had biopsies. All autopsy samples contained thymus tissue including one for which the biopsy had not contained graft. Of the six autopsies, one had evidence of thymopoiesis. Epithelium without thymopoiesis was seen in two of 25 biopsies in which thymus tissue was detected and in five of six autopsies. Graft rejection was seen in one autopsy. Biopsies were important for showing the following: 1) the damaging effect of pulse steroids on thymopoiesis; 2) the need for adequate immunosuppression of atypical subjects; and 3) the presence of thymopoiesis in the presence of ongoing immunosuppression. In addition, the biopsy could rule out graft rejection in the atypical subjects who had oligoclonal T cells that could cause rejection. In summary, combining biopsy and autopsy data, allogeneic thymus tissues showed thymopoiesis in 24 of 29 (86%) evaluable transplants. The results of these biopsies led to improved care of these complex patients.