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.

Immunological aspects of 22q11.2 deletion syndrome

“…T lymphocyte numbers are lower than normal for age, but naive T lymphocytes are present, indicating thymopoiesis, the cells proliferate when stimulated with PHA and there is a diverse T lymphocyte repertoire, which persists [34,[60][61][62]. Tolerance of recipient T lymphocytes to donor thymic tissue, has been demonstrated [63]. Subsequent to transplantation, tolerance to donor lymphocytes is also seen.…”

Immunologic reconstitution in 22q deletion (DiGeorge) syndrome

“…Clinically, this does not appear to be the case. Transplanted thymi clearly persist and are not rejected, and the T cells that develop in the thymic transplant setting show low reactivity against the thymus donor's T cells [7]. It has been postulated that the developing T cells could be selected by interaction with HLA molecules on fibroblasts from surrounding muscle tissue, which provide a set of appropriate HLA molecules with which positive and negative selection could occur [5].…”

Severe Combined Immunodeficiency Disorders

“…113 Recipients develop tolerance toward the grafts and third-party tissues HLA matched to the grafts. 128,129 Allogeneic thymus transplant results in overall survival of 73% 113,122,125 (100% for FOXN1 deficiency 113 ). In terms of long-term sequelae, approximately one-third of patients develop autoimmune thyroid disease for reasons that remain unclear.…”