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Diversity of NKR expression in aging T cells and in T cells of the aged: the new frontier into the exploration of protective immunity in the elderly. Exp Gerontol 2005 Jul;40(7):537-48

Date

07/09/2005

Pubmed ID

16002251

DOI

10.1016/j.exger.2005.04.012

Scopus ID

2-s2.0-23044510924   55 Citations

Abstract

Aging in the immune system is characterized by the contraction of the lymphocyte repertoire, exemplified by long-lived oligoclonal T cells that pervade the peripheral circulation. T-cell receptor (TCR) repertoire contraction likely explains the decline in immunity with chronological age as evidenced by the increased morbidity and mortality to common and new infections, and the low rates of protective responses to vaccination in the elderly. Interestingly, in vitro senescence models and cross sectional ex vivo studies have consistently demonstrated that senescent (or pre-senescent) T cells and T cells of the aged express unusually high densities of receptors that are normally found on natural killer (NK) cells, the killer cell immunoglobulin-like receptors (KIR) being the most diverse NK receptors (NKR). Molecular studies also show that T cells are programmed to express NKRs/KIRs, and T-cell clonal lineages express a variety of NKRs towards the end stages of their replicative lifespan. We propose that NKR/KIR induction in aging T cells is an adaptational diversification of the immune repertoire. We suggest that NKR/KIR expression in oligoclonal senescent and pre-senescent T cells is a compensatory adaptation to maintain immune competence despite the overall contraction in TCR diversity with aging. NKRs comprise a diverse superfamily of receptors. Mounting evidence for NKR/KIR signaling pathways in T cells divergent from those seen in NK cells indicate that senescent NKR(+)T cells are unique immune effectors. We suggest that appreciation of the functional diversity of these unusual NK-like T cells is central to the creative development of new strategies to enhance protective immunity in the aged.

Author List

Abedin S, Michel JJ, Lemster B, Vallejo AN

Author

Sameem Abedin MD Assistant Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adult
Aged, 80 and over
Aging
Antigens, CD
CD28 Antigens
Clone Cells
Gene Expression
Genotype
Humans
Immunity, Cellular
Infant, Newborn
Killer Cells, Natural
Phenotype
Receptors, Antigen, T-Cell
T-Lymphocytes