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

Area of Science:

• Immunology
• Transplantation Science
• Developmental Biology

Background:

• Complete DiGeorge anomaly results in severe immunodeficiency due to thymus aplasia.
• Thymus transplantation using allogeneic, HLA-nonmatched cultured tissue can restore immune function.
• The development of T cell tolerance towards the donor thymus graft has not been previously investigated.

Purpose of the Study:

• To investigate long-term T cell tolerance in recipients of thymus transplants for complete DiGeorge anomaly.
• To assess the immune response of recipients towards their HLA-nonmatched thymus allografts in vitro.

Main Methods:

• Mixed lymphocyte cultures (MLCs) were employed to evaluate immune reactivity.
• Peripheral blood mononuclear cells (PBMCs) from 12 thymus transplant recipients were tested against donor cells (thymus and peripheral blood) and third-party allogeneic cells.
• Proliferative responses were compared between recipients, adult controls, and responses to phytohemagglutinin.

Main Results:

• Recipients demonstrated significantly reduced reactivity towards donor thymus cells compared to third-party allogeneic cells (P=0.00007).
• Two subjects showed less reactivity to donor peripheral blood mononuclear cells than to third-party cells.
• Adult control PBMCs exhibited strong proliferation against donor thymic cells, unlike recipient PBMCs.

Conclusions:

• This study provides in vitro evidence of established, long-term tolerance in complete DiGeorge anomaly patients post-thymus transplantation.
• Recipient T cells exhibit tolerance towards their HLA-nonmatched thymus grafts, crucial for successful immunoreconstitution.