Poor T cell reconstitution following hematopoietic stem cell transplantation (HSCT) leads to susceptibility to tumor relapse and opportunistic infections. We are studying mechanisms contributing to T cell reconstitution following transplant, as well as methods to improve immune function in this setting.

We have previously demonstrated that adoptive transfer of in vitro-generated T cell precursors at the time of transplant leads to enhanced thymocyte and peripheral T cell numbers, resulting in significant anti-tumor and antimicrobial immunity post-HSCT. Our current work focuses on the extrathymic sites of T cell development following HSCT, and the mechanisms of T cell precursor trafficking. Additionally, we are utilizing lentiviral vectors to enhance the T cell reconstitution functions of in vitro-generated T cell precursors.

We are also investigating the role of CD4+CD3- lymphoid tissue-inducer (LTi) cells in the post-transplant setting. These cells are known to organize fetal lymphoid tissues and are increasingly being described in adult primary and secondary lymphoid organs. We are studying their effects on T cell reconstitution following HSCT, and their potential as therapeutic agents in this setting.