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.
Lemster
Bonnie H
BH
Department of Pediatrics, University of Pittsburgh, PA 15213, USA.
Michel
Joshua J
JJ
Montag
David T
DT
Paat
John J
JJ
Studenski
Stephanie A
SA
Newman
Anne B
AB
Vallejo
Abbe N
AN
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D019002:CD56 Antigen / Q000032:analysis / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D019002:CD56 Antigen; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D011948:Receptors, Antigen, T-Cell; D016159:Tumor Suppressor Protein p53