Journal
SEMINARS IN IMMUNOLOGY
Volume 24, Issue 5, Pages 365-372Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.smim.2012.04.003
Keywords
Aging; Signaling; T cell receptor; JAK STAT pathway; Dual-specific phosphatase
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Funding
- National Institutes of Health [U19 AI57266, U19 AI090019, R01 AR42527, R01 EY11916, R01 AI44142, P01 HL058000]
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With increasing age, the ability of the immune system to protect against new antigenic challenges or to control chronic infections erodes. Decline in thymic function and cumulating antigenic experiences of acute and chronic infections threaten T cell homeostasis, but insufficiently explain the failing immune competence and the increased susceptibility for autoimmunity. Alterations in signaling pathways in the aging T cells account for many of the age-related defects. Signaling threshold calibrations seen with aging frequently built on mechanisms that are operational in T cell development and T cell differentiation or are adaptations to the changing environment in the aging host. Age-related changes in transcription of receptors and signaling molecules shift the balance towards inhibitory pathways, most dominantly seen in CD8 T cells and to a lesser degree in CD4 T cells. Prominent examples are the expression of negative regulatory receptors of the CD28 and the TNF receptor superfamilies as well the expression of various cytoplasmic and nuclear dual-specific phosphatases. Published by Elsevier Ltd.
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