Age-related accumulation of T cells with markers of relatively stronger autoreactivity leads to functional erosion of T cells
Background Thymic involution is a prominent characteristic of an aging immune system. When thymic function is reduced/absent, the peripheral T cell pool is subject to the laws of peripheral T cell homeostasis that favor survival/expansion of T cell receptors with relatively higher functional avidity...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BioMed Central Ltd
2012
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| Online Access: | http://hdl.handle.net/1721.1/70114 |
| _version_ | 1826210350017544192 |
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| author | Tatari-Calderone, Zohreh Stojakovic, Milica Dewan, Ramita Le Bouder, Gama P. Jankovic, Dragana Vukmanovic, Stanislav |
| author2 | Sloan School of Management |
| author_facet | Sloan School of Management Tatari-Calderone, Zohreh Stojakovic, Milica Dewan, Ramita Le Bouder, Gama P. Jankovic, Dragana Vukmanovic, Stanislav |
| author_sort | Tatari-Calderone, Zohreh |
| collection | MIT |
| description | Background Thymic involution is a prominent characteristic of an aging immune system. When thymic function is reduced/absent, the peripheral T cell pool is subject to the laws of peripheral T cell homeostasis that favor survival/expansion of T cell receptors with relatively higher functional avidity for self-peptide/MHC complexes. Due to difficulties in assessing the TCR avidity in polyclonal population of T cells, it is currently not known whether high avidity T cells preferentially survive in aging individuals, and what impact this might have on the function of the immune system and development of autoimmune diseases. Results The phenotype of T cells from aged mice (18-24 months) indicating functional TCR avidity (CD3 and CD5 expression) correlates with the level of preserved thymic function. In mice with moderate thymic output (> 30% of peripheral CD62Lhi T cells), T cells displayed CD3lowCD5hi phenotype characteristic for high functional avidity. In old mice with drastically low numbers of CD62Lhi T cells reduced CD5 levels were found. After adult thymectomy, T cells of young mice developed CD3lowCD5hi phenotype, followed by a CD3lowCD5low phenotype. Spleens of old mice with the CD3low/CD5hi T cell phenotype displayed increased levels of IL-10 mRNA, and their T cells could be induced to secrete IL-10 in vitro. In contrast, downmodulation of CD5 was accompanied with reduced IL-10 expression and impaired anti-CD3 induced proliferation. Irrespective of the CD3/CD5 phenotype, reduced severity of experimental allergic myelitis occurred in old mice. In MTB TCRβ transgenic mice that display globally elevated TCR avidity for self peptide/MHC, identical change patterns occurred, only at an accelerated pace. Conclusions These findings suggest that age-associated dysfunctions of the immune system could in part be due to functional erosion of T cells devised to protect the hosts from the prolonged exposure to T cells with high-avidity for self. |
| first_indexed | 2024-09-23T14:48:24Z |
| format | Article |
| id | mit-1721.1/70114 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:48:24Z |
| publishDate | 2012 |
| publisher | BioMed Central Ltd |
| record_format | dspace |
| spelling | mit-1721.1/701142022-10-01T22:35:01Z Age-related accumulation of T cells with markers of relatively stronger autoreactivity leads to functional erosion of T cells Tatari-Calderone, Zohreh Stojakovic, Milica Dewan, Ramita Le Bouder, Gama P. Jankovic, Dragana Vukmanovic, Stanislav Sloan School of Management Le Bouder, Gama P. Background Thymic involution is a prominent characteristic of an aging immune system. When thymic function is reduced/absent, the peripheral T cell pool is subject to the laws of peripheral T cell homeostasis that favor survival/expansion of T cell receptors with relatively higher functional avidity for self-peptide/MHC complexes. Due to difficulties in assessing the TCR avidity in polyclonal population of T cells, it is currently not known whether high avidity T cells preferentially survive in aging individuals, and what impact this might have on the function of the immune system and development of autoimmune diseases. Results The phenotype of T cells from aged mice (18-24 months) indicating functional TCR avidity (CD3 and CD5 expression) correlates with the level of preserved thymic function. In mice with moderate thymic output (> 30% of peripheral CD62Lhi T cells), T cells displayed CD3lowCD5hi phenotype characteristic for high functional avidity. In old mice with drastically low numbers of CD62Lhi T cells reduced CD5 levels were found. After adult thymectomy, T cells of young mice developed CD3lowCD5hi phenotype, followed by a CD3lowCD5low phenotype. Spleens of old mice with the CD3low/CD5hi T cell phenotype displayed increased levels of IL-10 mRNA, and their T cells could be induced to secrete IL-10 in vitro. In contrast, downmodulation of CD5 was accompanied with reduced IL-10 expression and impaired anti-CD3 induced proliferation. Irrespective of the CD3/CD5 phenotype, reduced severity of experimental allergic myelitis occurred in old mice. In MTB TCRβ transgenic mice that display globally elevated TCR avidity for self peptide/MHC, identical change patterns occurred, only at an accelerated pace. Conclusions These findings suggest that age-associated dysfunctions of the immune system could in part be due to functional erosion of T cells devised to protect the hosts from the prolonged exposure to T cells with high-avidity for self. National Institutes of Health (U.S.) National Heart, Lung, and Blood Institute (1U54 HL090503 (ZT-C)) National Institute of Allergy and Infectious Diseases (U.S.) (Grant 1R01 AI48837) National Institute of Allergy and Infectious Diseases (U.S.) (Grant 1R01 AI41573 ) 2012-04-24T15:38:31Z 2012-04-24T15:38:31Z 2012-02 2011-11 2012-03-13T16:20:19Z Article http://purl.org/eprint/type/JournalArticle 1471-2172 http://hdl.handle.net/1721.1/70114 Tatari-Calderone, Zohreh et al. “Age-related Accumulation of T Cells with Markers of Relatively Stronger Autoreactivity Leads to Functional Erosion of T Cells.” BMC Immunology 13.1 (2012): 8. en http://dx.doi.org/10.1186/1471-2172-13-8 BMC Immunology Creative Commons Attribution http://creativecommons.org/licenses/by/2.0 Tatari-Calderone et al.; licensee BioMed Central Ltd. application/pdf BioMed Central Ltd BioMed Central Ltd |
| spellingShingle | Tatari-Calderone, Zohreh Stojakovic, Milica Dewan, Ramita Le Bouder, Gama P. Jankovic, Dragana Vukmanovic, Stanislav Age-related accumulation of T cells with markers of relatively stronger autoreactivity leads to functional erosion of T cells |
| title | Age-related accumulation of T cells with markers of relatively stronger autoreactivity leads to functional erosion of T cells |
| title_full | Age-related accumulation of T cells with markers of relatively stronger autoreactivity leads to functional erosion of T cells |
| title_fullStr | Age-related accumulation of T cells with markers of relatively stronger autoreactivity leads to functional erosion of T cells |
| title_full_unstemmed | Age-related accumulation of T cells with markers of relatively stronger autoreactivity leads to functional erosion of T cells |
| title_short | Age-related accumulation of T cells with markers of relatively stronger autoreactivity leads to functional erosion of T cells |
| title_sort | age related accumulation of t cells with markers of relatively stronger autoreactivity leads to functional erosion of t cells |
| url | http://hdl.handle.net/1721.1/70114 |
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