期刊
BONE MARROW TRANSPLANTATION
卷 50, 期 -, 页码 S77-S81出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/bmt.2015.101
关键词
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资金
- National Institutes of Health [R01-HL069929, R01-AI080455, R01-AI101406, P01-CA023766, 1K99CA176376]
- US National Institute of Allergy and Infectious Diseases (NIAID) [HHSN272200900059C]
- Experimental Therapeutics Center of MSKCC
- Lymphoma Foundation
- Alex's Lemonade Stand
- Geoffrey Beene Cancer Research Center at MSKCC
- Susan and Peter Solomon Divisional Genomics Program
- European Union [602587]
- Italian Foundation for Cancer Research
- Italian Society of Pharmacology
- American Society for Blood and Marrow Transplantation
- Australian National Health and Medical Research Council
- American Society of Hematology
- Associazione Italiana per la Ricerca sul Cancro Funding Source: Custom
Age-related decline in thymic function is a well-described process that results in reduced T-cell development and thymic output of new naive T cells. Thymic involution leads to reduced response to vaccines and new pathogens in otherwise healthy individuals; however, reduced thymic function is particularly detrimental in clinical scenarios where the immune system is profoundly depleted such as after chemotherapy, radiotherapy, infection and shock. Poor thymic function and restoration of immune competence has been correlated with an increased risk of opportunistic infections, tumor relapse and autoimmunity. Apart from their primary role in sex dimorphism, sex steroid levels profoundly affect the immune system in general and, in fact, age-related thymic involution has been at least partially attributed to the increase in sex steroids at puberty. Subsequently it has been demonstrated that the removal of sex steroids, or sex steroid ablation (SSA), triggers physiologic changes that ultimately lead to thymic re-growth and improved T-cell reconstitution in settings of hematopoietic stem cell transplant (HSCT). Although the cellular and molecular process underlying these regenerative effects are still poorly understood, SSA clearly represents an attractive therapeutic approach to enhance thymic function and restore immune competence in immunodeficient individuals.
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