NDLI: Sex steroid ablation enhances hematopoietic recovery following cytotoxic antineoplastic therapy in aged mice.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Goldberg, Gabrielle L. Chidgey, Ann P. Boyd, Richard L. Reiseger, Jessica J. Dudakov, Jarrod A. Vlahos, Katerina
Description	Country affiliation: Australia Author Affiliation: Dudakov JA ( Immune Regeneration Laboratory, Monash Immunology and Stem Cell Laboratories, Monash University, Wellington Road, Clayton VIC 3800, Australia. Jarrod.Dudakov@med.monash.edu.au)
Abstract	Cytotoxic antineoplastic therapy is widely used in the clinic as a treatment for malignant diseases. The treatment itself, however, leads to long-term depletion of the adaptive immune system, which is more pronounced in older patients, predominantly due to thymic atrophy. We and others have previously shown that withdrawal of sex steroids 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 steroid ablation (SSA) on the recovery of lymphopoiesis in the bone marrow (BM) and thymus following treatment with the chemotherapeutic agent cyclophosphamide (Cy) in middle-aged and old mice. 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.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	11
Volume Number	183
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2009-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Aging Physiology Antineoplastic Agents Adverse Effects Cyclophosphamide Gonadal Steroid Hormones Deficiency Lymphopoiesis Animals Bone Marrow Drug Effects Immunology Bone Marrow Cells Cytology Castration Enzyme-linked Immunosorbent Assay Flow Cytometry Hematopoietic Stem Cells Mice Mice, Inbred C57bl T-lymphocytes Thymus Gland Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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