Research ArticleTransplantation Tolerance

Inhibition of Transplantation Tolerance by Immune Senescence Is Reversed by Endocrine Modulation

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Science Translational Medicine  15 Jun 2011:
Vol. 3, Issue 87, pp. 87ra52
DOI: 10.1126/scitranslmed.3002270

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A Fountain of Youth for the Immune System

Raging hormones are often blamed for the sometimes erratic behavior of teenagers; yet, hormonal fluctuations aren’t saddled with the stigma they deserve for altering biological behaviors in older adults. An example of such a phenomenon is the senescent immune system, which responds poorly to new stimuli. This failure may stem in part from the shrinking of the thymus that begins by puberty (thymic involution). However, in contrast to what one might intuit, this age-related muting of the immune response does not improve tolerance induction and reduce rejection after cell or organ transplantation. Instead, an active immune system is required to promote tolerance to novel antigens. Zhao et al. now show that modifying hormone concentrations can restore the induction of transplant tolerance in aged mice.

The authors found that after the age of 12 months, mice became resistant to tolerance induction for cardiac transplants. However, surgical castration led to long-term graft acceptance and restoration of thymic cellularity. They then confirmed their findings with a procedure more likely to elicit patient assent—Lupron Depot injections, which temporarily disrupt gonadal function and are used clinically in prostate cancer care. This hormone-dependent transplant tolerance required the thymic production of regulatory T cells. Although it’s hard to extrapolate a mouse’s age to a human’s, these results suggest that hormone modification may improve transplant acceptance in older patients by restoring youthful exuberance to the immune system.


  • Citation: G. Zhao, D. J. Moore, J. I. Kim, K. M. Lee, M. R. O’Connor, P. E. Duff, M. Yang, J. Lei, J. F. Markmann, S. Deng, Inhibition of Transplantation Tolerance by Immune Senescence Is Reversed by Endocrine Modulation. Sci. Transl. Med. 3, 87ra52 (2011).

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