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* Department of Pediatrics,
Department of Medicine,
Department of Epidemiology,
Department of Immunology,
¶ Medical Student Training in Aging Research Program,
|| Pittsburgh Cancer Institute,
# Claude Pepper Older Americans Independence Center,
** Center for Aging and Population Health, and
McGowan Institute for Regenerative Medicine, University of Pittsburgh;
* Division of Rheumatology, Children’s Hospital of Pittsburgh, Pittsburgh, PA 15213; and
* Division of General Internal Medicine, Mayo Clinic, Rochester, MN 55905
All authors contributed to project design, conduct of research, recruitment of study participants, data analysis, and preparation of the manuscript, and meet criteria for authorship. A.N.V. had full access to all the data and takes full responsibility for integrity of the data and accuracy of data analysis.
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-
B 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by investigator-initiated research Grants R01AG022379 (to A.N.V.), R01AG023629 (to A.B.N.), and P30AG024827 (to S.A.S.) and by the University of Pittsburgh Cancer and Aging Program (P20CA103730) from the National Institutes of Health, and by the Department of Pediatrics, Children’s Hospital of Pittsburgh. D.T.M. was supported by the Pittsburgh Medical Student Training Program in Aging Research (T35-AG026778). The Children’s Hospital of Pittsburgh Rangos Research Center is a National Center for Research Resources-supported facility (C06-RR14489).
2 B.H.L. and J.J.M. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Abbe N. de Vallejo, University of Pittsburgh School of Medicine, Children’s Hospital Rangos Research Center, 3460 5th Avenue, Pittsburgh, PA 15213. E-mail address: andv26{at}pitt.edu
4 Abbreviation used in this paper: KIR, killer Ig-like receptor.
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