Our current research includes mechanistic studies of immune competence and tolerance in human transplantation.
Ongoing studies have been probing:
- how immune tolerance develops in HLA-mismatched UCBT recipients permitting withdrawal of all immunosuppressive drugs typically within the first year after transplantation. Clonal deletion besides peripheral regulatory networks have been interrogated and identified, Chen X. et al. manuscript in preparation 2020.
- how immune competence and tolerance will develop following tandem solid organ and subsequent bone marrow transplantations from the same unrelated, HLA-mismatched cadaveric donor. These patients suffer from pulmonary and infectious complications of a variety of primary immune deficiency diseases.
In 2009, Dr. Szabolcs and his collaborators were the first to demonstrate the feasibility and success of this concept in humans when a teenager with Artemis deficient SCID has become immune competent with a 4/8 HLA-matched unrelated donor derived BMT. In vitro hypo-reactivity was sustained after Treg depletion and was independent of IL-10 secretion, supporting the notion of clonal deletion as thymocytes of donor origin developed in the multiply HLA-mismatched host thymus from a T-cell depleted marrow graft. The University of Pittsburgh is the only center worldwide to offer such a clinical program.
Dr. Szabolcs leads a collaborative NIAID UO1 supported research program with members of the Department of Medicine, Immunology and the Starzl Institute as cadaveric vertebral marrow derived mucosal immunity and tolerance is analyzed in correlative mechanistic studies.