Age-related accumulation of T cells with markers of relatively stronger autoreactivity leads to functional erosion of T cells

Zohreh Tatari Calderone, Milica Stojakovic, Ramita Dewan, Gama Le Bouder, Dragana Jankovic, Stanislav Vukmanovic

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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 CD62L hi T cells), T cells displayed CD3 lowCD5 hi phenotype characteristic for high functional avidity. In old mice with drastically low numbers of CD62L hi T cells reduced CD5 levels were found. After adult thymectomy, T cells of young mice developed CD3 lowCD5 hi phenotype, followed by a CD3 lowCD5 low phenotype. Spleens of old mice with the CD3 low/CD5 hi 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.

Original languageEnglish
Article number8
JournalBMC Immunology
Volume13
DOIs
Publication statusPublished - 9 Feb 2012
Externally publishedYes

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T-Lymphocytes
Phenotype
Interleukin-10
Immune System
Myelitis
Thymectomy
Peptides
T-Cell Antigen Receptor
Transgenic Mice
Autoimmune Diseases
Homeostasis
Spleen
Messenger RNA
Population

ASJC Scopus subject areas

  • Immunology

Cite this

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; Bouder, Gama Le; Jankovic, Dragana; Vukmanovic, Stanislav.

In: BMC Immunology, Vol. 13, 8, 09.02.2012.

Research output: Contribution to journalArticle

Tatari Calderone, Zohreh ; Stojakovic, Milica ; Dewan, Ramita ; Bouder, Gama Le ; Jankovic, Dragana ; Vukmanovic, Stanislav. / Age-related accumulation of T cells with markers of relatively stronger autoreactivity leads to functional erosion of T cells. In: BMC Immunology. 2012 ; Vol. 13.
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