Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Jun 4:4:131.
doi: 10.3389/fimmu.2013.00131. eCollection 2013.

The janus head of T cell aging - autoimmunity and immunodeficiency

Jörg J Goronzy  1 , Guangjin Li, Zhen Yang, Cornelia M Weyand
Affiliations

The janus head of T cell aging - autoimmunity and immunodeficiency

Jörg J Goronzy et al. Front Immunol. .

Abstract

Immune aging is best known for its immune defects that increase susceptibility to infections and reduce adaptive immune responses to vaccination. In parallel, the aged immune system is prone to autoimmune responses and many autoimmune diseases increase in incidence with age or are even preferentially encountered in the elderly. Why an immune system that suboptimally responds to exogenous antigen fails to maintain tolerance to self-antigens appears to be perplexing. In this review, we will discuss age-associated deviations in the immune repertoire and the regulation of signaling pathways that may shed light on this conundrum.

Keywords: DNA damage response; T cell receptor signaling; autoimmunity; giant cell arteritis; immunosenescence; inflammation; pathogenesis; rheumatoid arthritis.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Key features of immunosenescence. Immune aging is a multifaceted process that generates a complex presentation of impaired adaptive immune responses, constitutive low-grade inflammation, and autoimmunity.
Figure 2
Figure 2
Comparison of immune aging manifestations and autoimmune pathomechanisms. The figure highlights mechanistic parallels between immune aging, animal models of autoimmune diseases, and human autoimmune diseases. Few selected animal models and human diseases representative of many others were chosen to illustrate the mechanistic path ways involved.
Figure 3
Figure 3
Molecular mechanism of accelerated immune aging. Rheumatoid arthritis is an autoimmune disease that is characterized by accelerated immune aging. The principle defects reside in impaired DNA repair responses.
See this image and copyright information in PMC

References

    1. Abedin S., Michel J. J., Lemster B., Vallejo A. N. (2005). Diversity of NKR expression in aging T cells and in T cells of the aged: the new frontier into the exploration of protective immunity in the elderly. Exp. Gerontol. 40, 537–54810.1016/j.exger.2005.04.012 - DOI - PubMed
    1. Altan-Bonnet G., Germain R. N. (2005). Modeling T cell antigen discrimination based on feedback control of digital ERK responses. PLoS Biol. 3:e356.10.1371/journal.pbio.0030356 - DOI - PMC - PubMed
    1. Armanios M. (2013). Telomeres and age-related disease: how telomere biology informs clinical paradigms. J. Clin. Invest. 123, 996–100210.1172/JCI66370 - DOI - PMC - PubMed
    1. Bettini M. L., Kersh G. J. (2007). MAP kinase phosphatase activity sets the threshold for thymocyte positive selection. Proc. Natl. Acad. Sci. U.S.A. 104, 16257–1626210.1073/pnas.0705321104 - DOI - PMC - PubMed
    1. Billadeau D. D., Upshaw J. L., Schoon R. A., Dick C. J., Leibson P. J. (2003). NKG2D-DAP10 triggers human NK cell-mediated killing via a Syk-independent regulatory pathway. Nat. Immunol. 4, 557–56410.1038/ni929 - DOI - PubMed

LinkOut - more resources