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.
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