ArticleScience translational medicine2011
Inhibition of transplantation tolerance by immune senescence is reversed by endocrine modulation.
Article in Science translational medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- Review
- Metronidazole-mediated gut anaerobe remodeling is associated with transplant rejection.Frontiers in cellular and infection microbiology · 2026Article
- Impact of Donor and Recipient Sex on Long-Term Outcomes Following Living Donor Kidney Transplantation: A Retrospective Dual-Center Study.Clinical transplantation · 2025Observational
- Development and validation of AI-based automatic segmentation and measurement of thymus on chest CT scans.BMC medical imaging · 2025Article
- Outcomes of Primary Simultaneous Pancreas-kidney Transplants by Induction Agent in the United States.Transplantation direct · 2022Article
- Mettl14-mediated m6A modification enhances the function of Foxp3Frontiers in immunology · 2022Article
- In Experimental Dilated Cardiomyopathy Heart Failure and Survival Are Adversely Affected by a Lack of Sexual Interactions.International journal of molecular sciences · 2020Article
- Aging and the immune response to organ transplantation.The Journal of clinical investigation · 2017Review
- Differences in Hypercholesterolemia and Atherogenesis Induced by Common Androgen Deprivation Therapies in Male Mice.Journal of the American Heart Association · 2016Article
- Elevated levels of interferon-γ production by memory T cells do not promote transplant tolerance resistance in aged recipients.PloS one · 2013Article
- An age-specific CD8+ T cell pathway that impairs the effectiveness of strategies to prolong allograft survival.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- Castration reverses immunosenescence in aged mice.Acta pharmacologica Sinica · 2011Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The senescent immune system responds poorly to new stimuli; thymic involution, accumulation of memory cells against other specificities, and general refractoriness to antigen signaling all may contribute to poor resistance to infection. These same changes may pose a significant clinical barrier to organ transplantation, as transplantation tolerance requires thymic participation and integrated, tolerance-promoting responses to novel antigens. We found that after the age of 12 months, mice became resistant to the tolerance-inducing capacity of the monoclonal antibody therapy anti-CD45RB. This resistance to tolerance to cardiac allografts could be overcome by surgical castration of male mice, a procedure that led to thymic regeneration and long-term graft acceptance. The potential for clinical translation of this endocrine-immune interplay was confirmed by the ability of Lupron Depot injections, which temporarily disrupt gonadal function, to restore tolerance in aged mice. Furthermore, we demonstrated that the restoration of tolerance after surgical or chemical castration depended on thymic production of regulatory T cells (T(regs)); thymectomy or T(reg) depletion abrogated tolerance restoration. The aging of the immune system ("immune senescence") is a significant barrier to immune tolerance, but this barrier can be overcome by targeting sex steroid production with commonly used clinical therapeutics.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.