Immune aging and autoimmunity

Abstract

Age is an important risk for autoimmunity, and many autoimmune diseases preferentially occur in the second half of adulthood when immune competence has declined and thymic T cell generation has ceased. Many tolerance checkpoints have to fail for an autoimmune disease to develop, and several of those are susceptible to the immune aging process. Homeostatic T cell proliferation which is mainly responsible for T cell replenishment during adulthood can lead to the selection of T cells with increased affinity to self- or neoantigens and enhanced growth and survival properties. These cells can acquire a memory-like phenotype, in particular under lymphopenic conditions. Accumulation of end-differentiated effector T cells, either specific for self-antigen or for latent viruses, have a low activation threshold due to the expression of signaling and regulatory molecules and generate an inflammatory environment with their ability to be cytotoxic and to produce excessive amounts of cytokines and thereby inducing or amplifying autoimmune responses.

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Abbreviations

ATM:

Ataxia telangiectasia mutated

CMV:

Cytomegalovirus

HAART:

Highly active antiretroviral therapy

IRIS:

Immune reconstitution inflammatory syndrome

KIR:

Killer immunoglobulin-like receptors

TREC:

T cell receptor excision circle

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Acknowledgments

This work was supported by grants from the National Institutes of Health (AI 57266 and AI 90019).

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Correspondence to Jörg J. Goronzy.

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Goronzy, J.J., Weyand, C.M. Immune aging and autoimmunity. Cell. Mol. Life Sci. 69, 1615–1623 (2012). https://doi.org/10.1007/s00018-012-0970-0

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Keywords

  • Age
  • Autoimmunity
  • T cell memory
  • T cell homeostasis
  • CD45RA T effector cells