The thymus plays an important role in maintaining the peripheral T cell pool in human adults and in immune reconstitution after stem cell transplantation. However, no treatment strategy is currently available to augment postnatal human thymus output following stem cell transplantation in a manner analogous to G-CSF for augmentation of myeloid reconstitution. The lack of an assay for postnatal thymic function has also hindered the study of modalities that might stimulate renewed or augmented thymopoiesis in vivo., These numbers of stem cells to repopulate the human immune systems in adults, thus making allogeneic transplantation using cord blood stem cells available to a wide variety of recipients. Measurement of T Cell Receptor Delta (TCRD) signal joint (sj) T cell receptor excision circles (TRECs) has been used to quantify and monitor human thymic output following highly active anti-retroviral therapy (HAART) in HIV-infected patients. We have recently used the TREC assay to monitor human thymic output before and after thymectomy for myasthenia gravis (MG) and to monitor immune reconstitution following thymus transplantation for DiGeorge Syndrome and bone marrow transplantation for Severe Combined Immune Deficiency Syndrome (SCID). No TREC assay was previously available for murine studies. We have developed a TCRD sjTREC assay to monitor thymic output in mice, and have begun to apply it to study murine postnatal thymic function. In the specific aims below, we will combine (molecular) sjTREC, histologic, and phenotypic analysis of T cells and thymus tissues to devise and evaluate new strategies for enhancing T cell immune reconstitution in the setting of stem cell transplantation.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
Project #
Application #
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Duke University
United States
Zip Code
Zhang, Ping; Wu, Jieying; Deoliveira, Divino et al. (2012) Allospecific CD4(+) effector memory T cells do not induce graft-versus-host disease in mice. Biol Blood Marrow Transplant 18:1488-99
Szabolcs, Paul (2011) T-lymphocyte recovery and function after cord blood transplantation. Immunol Res 49:56-69
Szabolcs, Paul; Cairo, Mitchell S (2010) Unrelated umbilical cord blood transplantation and immune reconstitution. Semin Hematol 47:22-36
Szabolcs, Paul (2010) The immunobiology of cord blood transplantation. Korean J Hematol 45:224-35
Kurtzberg, Joanne (2009) Update on umbilical cord blood transplantation. Curr Opin Pediatr 21:22-9
Szabolcs, Paul; Niedzwiecki, Donna (2008) Immune reconstitution in children after unrelated cord blood transplantation. Biol Blood Marrow Transplant 14:66-72
Mazur, Melissa A; Davis, Craig C; Szabolcs, Paul (2008) Ex vivo expansion and Th1/Tc1 maturation of umbilical cord blood T cells by CD3/CD28 costimulation. Biol Blood Marrow Transplant 14:1190-6
Urs, Nikhil M; Kowalczyk, Andrew P; Radhakrishna, Harish (2008) Different mechanisms regulate lysophosphatidic acid (LPA)-dependent versus phorbol ester-dependent internalization of the LPA1 receptor. J Biol Chem 283:5249-57
Hudson, Lori L; Louise Markert, M; Devlin, Blythe H et al. (2007) Human T cell reconstitution in DiGeorge syndrome and HIV-1 infection. Semin Immunol 19:297-309
Szabolcs, P; Niedzwiecki, D (2007) Immune reconstitution after unrelated cord blood transplantation. Cytotherapy 9:111-22

Showing the most recent 10 out of 21 publications