Long-term tolerance to allogeneic thymus transplants in complete DiGeorge anomaly

Abstract

Thymus transplantation in subjects with complete DiGeorge anomaly using postnatal allogeneic HLA-nonmatched cultured thymus tissue provides immunoreconstitution. Tolerance of the newly developed T cells toward the donor thymus has not previously been studied. Mixed lymphocyte cultures were used to test 12 thymus transplant recipients for long-term tolerance toward their thymus allografts. Two subjects tested for responses toward thymus donor peripheral blood mononuclear cells showed significantly less reactivity toward the donors compared to responses against third-party allogeneic cells. Peripheral blood mononuclear cells from 10 other subjects were less responsive toward cryopreserved donor thymic cells than toward allogeneic cells (P=0.00007). Adult control peripheral blood mononuclear cells proliferated strongly in response to the donor thymic cells. Both the subjects and controls showed similar proliferative responses against allogeneic cells and phytohemagglutinin. This study provides in vitro evidence for long-term tolerance of complete DiGeorge anomaly thymus transplantation recipients toward their HLA-nonmatched thymus grafts.

Figure 1. Proliferation studies

Patient results (P) are shown compared to healthy adult controls (C). Symbols denote individual subject and corresponding control responses toward the stimuli listed at the top of each column for a given experiment; median values are shown by the horizontal bars (—). DIG105 (□) had the same sample of PBMCs tested twice. DIG120 (■) had multiple control samples tested in the same assay (see text). Responses are measured by ³H-thymidine incorporation shown in counts per minute. (*) = P < 0.05, (**) = P < 0.005, (***) = P < 0.00001, NS = P ≥ 0.05.