Elevated Levels of Interferon-γ Production by Memory T Cells Do Not Promote Transplant Tolerance Resistance in Aged Recipients

Immunosenescence predisposes the elderly to infectious and autoimmune diseases and impairs the response to vaccination. We recently demonstrated that ageing also impedes development of transplantation tolerance. Unlike their young counterparts (8-12 weeks of age) aged male recipients (greater than 1...

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Main Authors:	Kim, James I., Stott, Ryan T., Soohoo, Julie, Lee, Kang Mi, Zhao, Gaoping, Yeh, Heidi, Deng, Shaoping, Markmann, James F.
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858330/

id	pubmed-3858330
recordtype	oai_dc
spelling	pubmed-38583302013-12-11 Elevated Levels of Interferon-γ Production by Memory T Cells Do Not Promote Transplant Tolerance Resistance in Aged Recipients Kim, James I. Stott, Ryan T. Soohoo, Julie Lee, Kang Mi Zhao, Gaoping Yeh, Heidi Deng, Shaoping Markmann, James F. Research Article Immunosenescence predisposes the elderly to infectious and autoimmune diseases and impairs the response to vaccination. We recently demonstrated that ageing also impedes development of transplantation tolerance. Unlike their young counterparts (8-12 weeks of age) aged male recipients (greater than 12 months of age) transplanted with a full MHC-mismatched heart are resistant to tolerance mediated by anti-CD45RB antibody. Surprisingly, either chemical or surgical castration restored tolerance induction to levels observed using young recipients. Based on the strong impact of endocrine modulation on transplant tolerance, we explored the impact of ageing and castration on the immune system. Here we report a significant increase in the percentage of T cells that produce interferon-γ (IFN-γ) in aged male versus young male animals and that the overall increase in IFN-γ production was due to an expansion of IFN-γ-producing memory T cells in aged animals. In contrast to IFN-γ production, we did not observe differences in IL-10 expression in young versus old male mice. We hypothesized that endocrine modulation would diminish the elevated levels of IFN-γ production in aged recipients, however, we observed no significant reduction in the percentage of IFN-γ+ T cells upon castration. Furthermore, we neutralized interferon-γ by antibody and did not observe an effect on graft survival. We conclude that while elevated levels of interferon-γ serves as a marker of tolerance resistance in aged mice, other as yet to be identified factors are responsible for its cause. Defining these factors may be relevant to design of tolerogenic strategies for aged recipients. Public Library of Science 2013-12-10 /pmc/articles/PMC3858330/ /pubmed/24340063 http://dx.doi.org/10.1371/journal.pone.0082856 Text en © 2013 Kim et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Kim, James I. Stott, Ryan T. Soohoo, Julie Lee, Kang Mi Zhao, Gaoping Yeh, Heidi Deng, Shaoping Markmann, James F.
spellingShingle	Kim, James I. Stott, Ryan T. Soohoo, Julie Lee, Kang Mi Zhao, Gaoping Yeh, Heidi Deng, Shaoping Markmann, James F. Elevated Levels of Interferon-γ Production by Memory T Cells Do Not Promote Transplant Tolerance Resistance in Aged Recipients
author_facet	Kim, James I. Stott, Ryan T. Soohoo, Julie Lee, Kang Mi Zhao, Gaoping Yeh, Heidi Deng, Shaoping Markmann, James F.
author_sort	Kim, James I.
title	Elevated Levels of Interferon-γ Production by Memory T Cells Do Not Promote Transplant Tolerance Resistance in Aged Recipients
title_short	Elevated Levels of Interferon-γ Production by Memory T Cells Do Not Promote Transplant Tolerance Resistance in Aged Recipients
title_full	Elevated Levels of Interferon-γ Production by Memory T Cells Do Not Promote Transplant Tolerance Resistance in Aged Recipients
title_fullStr	Elevated Levels of Interferon-γ Production by Memory T Cells Do Not Promote Transplant Tolerance Resistance in Aged Recipients
title_full_unstemmed	Elevated Levels of Interferon-γ Production by Memory T Cells Do Not Promote Transplant Tolerance Resistance in Aged Recipients
title_sort	elevated levels of interferon-γ production by memory t cells do not promote transplant tolerance resistance in aged recipients
description	Immunosenescence predisposes the elderly to infectious and autoimmune diseases and impairs the response to vaccination. We recently demonstrated that ageing also impedes development of transplantation tolerance. Unlike their young counterparts (8-12 weeks of age) aged male recipients (greater than 12 months of age) transplanted with a full MHC-mismatched heart are resistant to tolerance mediated by anti-CD45RB antibody. Surprisingly, either chemical or surgical castration restored tolerance induction to levels observed using young recipients. Based on the strong impact of endocrine modulation on transplant tolerance, we explored the impact of ageing and castration on the immune system. Here we report a significant increase in the percentage of T cells that produce interferon-γ (IFN-γ) in aged male versus young male animals and that the overall increase in IFN-γ production was due to an expansion of IFN-γ-producing memory T cells in aged animals. In contrast to IFN-γ production, we did not observe differences in IL-10 expression in young versus old male mice. We hypothesized that endocrine modulation would diminish the elevated levels of IFN-γ production in aged recipients, however, we observed no significant reduction in the percentage of IFN-γ+ T cells upon castration. Furthermore, we neutralized interferon-γ by antibody and did not observe an effect on graft survival. We conclude that while elevated levels of interferon-γ serves as a marker of tolerance resistance in aged mice, other as yet to be identified factors are responsible for its cause. Defining these factors may be relevant to design of tolerogenic strategies for aged recipients.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858330/
_version_	1612037071452504064

Elevated Levels of Interferon-γ Production by Memory T Cells Do Not Promote Transplant Tolerance Resistance in Aged Recipients

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