Induction of CD56 and TCR-independent activation of T cells with aging.
Degeneration of the thymus and severe contraction of the T cell repertoire with aging suggest that immune homeostasis in old age could be mediated by distinct effectors. Therefore, receptors expressed on T cells as they undergo senescence in vitro, as well as those displayed by circulating T cells during normal chronologic aging, were examined. Monitoring of T cells driven to senescence showed de novo induction of CD56, the prototypic receptor of NK cells. Analysis of fresh T cells in peripheral blood showed an age-dependent induction of CD56. These unusual T cells expressed high levels of Bcl2, p16, and p53, and had limited, or completely lost, ability to undergo cell division, properties consistent with senescence. CD56 cross-linking without TCR ligation on CD56(+) T cells resulted in extensive protein phosphorylation, NF-kappaB activation, and Bax down-regulation. CD56 cross-linking was also sufficient to drive production of various humoral factors. These data suggest that the immunologic environment in old age is functionally distinct, rather than being a dysfunctional version of that seen at a young age. CD56(+) T cells are unique effectors capable of mediating TCR-independent immune cascades that could be harnessed to enhance protective immunity in the elderly.
Duke Scholars
Altmetric Attention Stats
Dimensions Citation Stats
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tumor Suppressor Protein p53
- T-Lymphocytes
- Receptors, Antigen, T-Cell
- Proto-Oncogene Proteins c-bcl-2
- NF-kappa B
- Middle Aged
- Male
- Lymphocyte Activation
- Immunology
- Humans
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tumor Suppressor Protein p53
- T-Lymphocytes
- Receptors, Antigen, T-Cell
- Proto-Oncogene Proteins c-bcl-2
- NF-kappa B
- Middle Aged
- Male
- Lymphocyte Activation
- Immunology
- Humans