Most studies evaluating immune reconstitution following hematopoietic stem cell transplantation (HSCT) have focused on immunophenotypic analysis and the capacity of the immune system to respond to mitogenic stimulation. However, protection against infectious pathogens and potentially anti-tumor responses correlate with the presence of antigen-specific immunity, not the immunophenotypic presence of T lymphocytes. Antigen-specific T lymphocytes present after HSCT can be derived from donor antigen-specific T lymphocytes present in the transplantation inoculum if it is not T cell depleted. Furthermore, the naive T lymphocytes contained in the HSCT inoculum have the potential to develop into antigen-specific T lymphocytes. If the transplantation inoculum is T cell depleted, then all antigen-specific T lymphocytes will have to be derived from the newly engrafted hematopoietic stem cells following their differentiation through the recipient thymus. Thus, defects in thymopoiesis will result in delays or the absence of naive T lymphocytes and ultimately defects in antigen-specific immunity.
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