Thymus transplantation

Abstract

Thymus transplantation is a promising investigational therapy for infants born with no thymus. Because of the athymia, these infants lack T cell development and have a severe primary immunodeficiency. Although thymic hypoplasia or aplasia is characteristic of DiGeorge anomaly, in "complete" DiGeorge anomaly, there is no detectable thymus as determined by the absence of naive (CD45RA(+), CD62L(+)) T cells. Transplantation of postnatal allogeneic cultured thymus tissue was performed in sixty subjects with complete DiGeorge anomaly who were under the age of 2 years. Recipient survival was over 70%. Naive T cells developed 3-5 months after transplantation. The graft recipients were able to discontinue antibiotic prophylaxis, and immunoglobulin replacement. Immunosuppression was used in a subset of subjects but was discontinued when naive T cells developed. The adverse events have been acceptable with thyroid disease being the most common. Research continues on mechanisms underlying immune reconstitution after thymus transplantation.

Figure 1

Kaplan Meier survival curve of subjects with complete DiGeorge anomaly who underwent thymus transplantation. Forty three of sixty transplanted subjects survive.

Figure 2

Naïve CD4⁺ and CD8⁺ T cell counts after thymus transplantation. Each subject’s data are on a single line. The 10^th and 90^th percentiles for children of this age in years are indicated by the dashed bold lines, the mean is indicated by the solid bold line. [39] All subjects who survive over 1 year after transplantation are included. The left panels include the subjects who did not receive peritransplantation immunosuppression; the right panels include the subjects who did receive peritransplantation immunosuppression.

Figure 3

T cell proliferative responses to soluble CD3 and tetanus toxoid after thymus transplantation. The responses to soluble CD3 are in the upper panels and responses to tetanus toxoid are in the lower panels. The responses to tetanus toxoid include time points before and after immunization with tetanus toxoid. The subjects who received immunosuppression are on the right and those without immunosuppression are on the left. All subjects who have been tested are shown. The mean and 2 standard deviations (2SD) below the mean (calculated with log transformed data) are based on the healthy adult volunteers run in these assays.

Figure 4

Production of anti-A and anti-B isohemagglutinins. The left panel includes subjects who are not blood group A and did not receive a blood group A thymus. The right panel includes subjects who are not blood group B and did not receive a blood group B thymus. For inclusion in this figure, subjects had to be tested past 2 years after transplantation. A total of 30 subjects were tested past 2 years after transplantation. Each subject is represented by a separate line or marker. Normal values are those above the solid bold line in each graph.