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Functionally Diverse NK-Like T Cells Are Effectors and Predictors of Successful Aging

View Article: PubMed Central - PubMed

ABSTRACT

The fundamental challenge of aging and long-term survivorship is maintenance of functional independence and compression of morbidity despite a life history of disease. Inasmuch as immunity is a determinant of individual health and fitness, unraveling novel mechanisms of immune homeostasis in late life is of paramount interest. Comparative studies of young and old persons have documented age-related atrophy of the thymus, the contraction of diversity of the T cell receptor (TCR) repertoire, and the intrinsic inefficiency of classical TCR signaling in aged T cells. However, the elderly have highly heterogeneous health phenotypes. Studies of defined populations of persons aged 75 and older have led to the recognition of successful aging, a distinct physiologic construct characterized by high physical and cognitive functioning without measurable disability. Significantly, successful agers have a unique T cell repertoire; namely, the dominance of highly oligoclonal αβT cells expressing a diverse array of receptors normally expressed by NK cells. Despite their properties of cell senescence, these unusual NK-like T cells are functionally active effectors that do not require engagement of their clonotypic TCR. Thus, NK-like T cells represent a beneficial remodeling of the immune repertoire with advancing age, consistent with the concept of immune plasticity. Significantly, certain subsets are predictors of physical/cognitive performance among older adults. Further understanding of the roles of these NK-like T cells to host defense, and how they integrate with other physiologic domains of function are new frontiers for investigation in Aging Biology. Such pursuits will require a research paradigm shift from the usual young-versus-old comparison to the analysis of defined elderly populations. These endeavors may also pave way to age-appropriate, group-targeted immune interventions for the growing elderly population.

No MeSH data available.


Diagrammatic comparison between conventional CD28+ and senescent CD28 NK-like T cells. This illustration summarizes findings from various investigators as described in the text. The diagram shown was modified from (32) with permission from Aging and Disease journal under the terms of Creative Commons Attribution License (CC BY). This license allows the unrestricted use, distribution, modification, and reproduction in any medium by the author with credited citation of the original publication.
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Figure 1: Diagrammatic comparison between conventional CD28+ and senescent CD28 NK-like T cells. This illustration summarizes findings from various investigators as described in the text. The diagram shown was modified from (32) with permission from Aging and Disease journal under the terms of Creative Commons Attribution License (CC BY). This license allows the unrestricted use, distribution, modification, and reproduction in any medium by the author with credited citation of the original publication.

Mentions: The array of NK-related receptors expressed on aged CD28 T cells is summarized in Figure 1. They include the prototypic stimulatory NK receptors, CD16, CD56, and NKG2D. They may also express CD161, and various inhibitory NK receptors such as CD94 and NKG2A, and members of the CD158 killer cell immunoglobulin-like receptor family (12, 50, 69, 72, 77, 88–90). Unlike the selective single allelic expression for TCR, NK-related receptors are expressed co-dominantly on aged T cells.


Functionally Diverse NK-Like T Cells Are Effectors and Predictors of Successful Aging
Diagrammatic comparison between conventional CD28+ and senescent CD28 NK-like T cells. This illustration summarizes findings from various investigators as described in the text. The diagram shown was modified from (32) with permission from Aging and Disease journal under the terms of Creative Commons Attribution License (CC BY). This license allows the unrestricted use, distribution, modification, and reproduction in any medium by the author with credited citation of the original publication.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121286&req=5

Figure 1: Diagrammatic comparison between conventional CD28+ and senescent CD28 NK-like T cells. This illustration summarizes findings from various investigators as described in the text. The diagram shown was modified from (32) with permission from Aging and Disease journal under the terms of Creative Commons Attribution License (CC BY). This license allows the unrestricted use, distribution, modification, and reproduction in any medium by the author with credited citation of the original publication.
Mentions: The array of NK-related receptors expressed on aged CD28 T cells is summarized in Figure 1. They include the prototypic stimulatory NK receptors, CD16, CD56, and NKG2D. They may also express CD161, and various inhibitory NK receptors such as CD94 and NKG2A, and members of the CD158 killer cell immunoglobulin-like receptor family (12, 50, 69, 72, 77, 88–90). Unlike the selective single allelic expression for TCR, NK-related receptors are expressed co-dominantly on aged T cells.

View Article: PubMed Central - PubMed

ABSTRACT

The fundamental challenge of aging and long-term survivorship is maintenance of functional independence and compression of morbidity despite a life history of disease. Inasmuch as immunity is a determinant of individual health and fitness, unraveling novel mechanisms of immune homeostasis in late life is of paramount interest. Comparative studies of young and old persons have documented age-related atrophy of the thymus, the contraction of diversity of the T cell receptor (TCR) repertoire, and the intrinsic inefficiency of classical TCR signaling in aged T cells. However, the elderly have highly heterogeneous health phenotypes. Studies of defined populations of persons aged 75 and older have led to the recognition of successful aging, a distinct physiologic construct characterized by high physical and cognitive functioning without measurable disability. Significantly, successful agers have a unique T cell repertoire; namely, the dominance of highly oligoclonal αβT cells expressing a diverse array of receptors normally expressed by NK cells. Despite their properties of cell senescence, these unusual NK-like T cells are functionally active effectors that do not require engagement of their clonotypic TCR. Thus, NK-like T cells represent a beneficial remodeling of the immune repertoire with advancing age, consistent with the concept of immune plasticity. Significantly, certain subsets are predictors of physical/cognitive performance among older adults. Further understanding of the roles of these NK-like T cells to host defense, and how they integrate with other physiologic domains of function are new frontiers for investigation in Aging Biology. Such pursuits will require a research paradigm shift from the usual young-versus-old comparison to the analysis of defined elderly populations. These endeavors may also pave way to age-appropriate, group-targeted immune interventions for the growing elderly population.

No MeSH data available.