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

Authors

Zohreh Tatari-Calderone, George Washington University
Milica Stojakovic, Children's National Medical Center, Washington, DC
Ramita Dewan, Children's National Medical Center, Washington, DC
Gama L. Bouder, Children's National Medical Center, Washington, DC
Dragana Jankovic, National Institutes of Health, Bethesda, MD
Stanislav Vukmanovic, George Washington University

Document Type

Journal Article

Publication Date

2-9-2013

Journal

BMC Immunology

Volume

Volume 13

Inclusive Pages

Article number 8

Keywords

Aging--immunology; Aging--pathology; T-Lymphocytes--immunology; T-Lymphocytes--pathology

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.

Comments

BMC Immunology

PMCID: PMC3305419

Creative Commons License

This work is licensed under a Creative Commons Attribution 3.0 License.

APA Citation

Tatari-Calderone, Z., Stojakovic, M., Dewan, R., Bouder, G. L., Jankovic, D., & Vukmanovic, S. (2012). Age-related accumulation of T cells with markers of relatively stronger autoreactivity leads to functional erosion of T cells. BMC Immunology, 13.

Peer Reviewed

1

Open Access

1