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Logo of bmcimmBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Immunology
 
BMC Immunol. 2012; 13: 8.
Published online Feb 9, 2012. doi:  10.1186/1471-2172-13-8
PMCID: PMC3305419
Age-related accumulation of T cells with markers of relatively stronger autoreactivity leads to functional erosion of T cells
Zohreh Tatari-Calderone,1 Milica Stojakovic,1,2 Ramita Dewan,1 Gama Le Bouder,1 Dragana Jankovic,3 and Stanislav Vukmanoviccorresponding author1,2,4
1Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center, Washington, DC, USA
2Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Medical Center, Washington, DC, USA
3Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
4Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010-2970, USA
corresponding authorCorresponding author.
Zohreh Tatari-Calderone: ztatari/at/cnmc.org; Milica Stojakovic: mstojako/at/cnmc.org; Ramita Dewan: ramita.dewan/at/gmail.com; Gama Le Bouder: lebouder/at/MIT.edu; Dragana Jankovic: DJankovic/at/niaid.nih.gov; Stanislav Vukmanovic: svukmano/at/cnmc.org
Received November 1, 2011; Accepted February 9, 2012.
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 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.
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