Sex XXXX ablation enhances hematopoietic recovery following cytotoxic antineoplastic therapy in aged @entity19 .

@entity1 @entity5 @entity19 @entity786 @entity134 @entity194 @entity230
Cytotoxic antineoplastic therapy is widely used in the clinic as a treatment for @entity5 . The treatment itself, however, leads to long-term depletion of the adaptive immune system, which is more pronounced in older @entity1 , predominantly due to thymic @entity194 . We and others have previously shown that withdrawal of sex @entity230 is able to regenerate the aged thymus and enhance recovery from autologous and allogeneic hematopoietic stem cell transplant. In this study we have examined the effects of sex @entity134 ablation (SSA) on the recovery of lymphopoiesis in the bone marrow (BM) and thymus following treatment with the chemotherapeutic agent @entity786 (Cy) in middle-aged and old @entity19 . Furthermore, we have also examined the impact of this regeneration on peripheral immunity. SSA enhanced the recovery of BM resident hematopoietic stem cells and lymphoid progenitors and promoted lymphopoiesis. Interestingly, Cy alone caused a profound increase in the recently described common lymphoid progenitor 2 (CLP-2) population in the BM. In the thymus, SSA caused a profound increase in cellularity as well as all intrathymic T-lineage progenitors including early T-lineage progenitors (ETPs) and non-canonical T cell progenitors such as the CLP-2. We also found that these transferred into numerical increases in the periphery with enhanced B and T cell numbers. Furthermore, these lymphocytes were found to have an enhanced functional capacity with no perturbation of the TCR repertoire. Taken together, these results provide the basis for the use of SSA in the clinic to enhance treatment outcomes from cytotoxic antineoplastic therapy.
