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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.


Related in: MedlinePlus

NK-like T cells are linked to high cognitive and physical function. Data shown are 3D scatter plot summaries from the re-analyses of our data from the All Stars cohort of the Cardiovascular Health Study (70). CD16 and CD56 expression on CD4+ CD28 and CD8+ CD28 T cells are expressed as GMFI, which was determined by multicolor flow cytometry. Older adults were grouped as unimpaired (solid triangles) or impaired (open circles) based on a simple criterion of ADL = 0 and ADL > 1, respectively. Measurements of 3MS cognition score and gait speed and ADL scoring are as described in the text.
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Figure 2: NK-like T cells are linked to high cognitive and physical function. Data shown are 3D scatter plot summaries from the re-analyses of our data from the All Stars cohort of the Cardiovascular Health Study (70). CD16 and CD56 expression on CD4+ CD28 and CD8+ CD28 T cells are expressed as GMFI, which was determined by multicolor flow cytometry. Older adults were grouped as unimpaired (solid triangles) or impaired (open circles) based on a simple criterion of ADL = 0 and ADL > 1, respectively. Measurements of 3MS cognition score and gait speed and ADL scoring are as described in the text.

Mentions: Another way to illustrate the relationship between NK-like CD28 T cells and physical/cognitive functioning is shown in Figure 2 with a three dimensional plot for CD16 or CD56 expression levels (measured as GMFI, geometric mean fluorescence intensity), 3MS cognition score, and gait speed. The latter measure of physical function was determined by a 4-m walk test that has been standardized/validated from various cohort studies (16, 176). The data show a clear segregation between the high functioning and functionally impaired elders. This is surprising given that “impaired” and “unimpaired” categories in this graphical illustration are very loosely defined by ADL ≥ 1 and ADL = 0, respectively. Therefore, it will be of significant interest to determine if this three-way relationship between subsets of NK-like T cells, physical function, and cognitive ability translates into vigorous immune defense. In addition, the underlying mechanistic link(s) between these three physiologic systems will be instructive about integrative physiology of successful aging.


Functionally Diverse NK-Like T Cells Are Effectors and Predictors of Successful Aging
NK-like T cells are linked to high cognitive and physical function. Data shown are 3D scatter plot summaries from the re-analyses of our data from the All Stars cohort of the Cardiovascular Health Study (70). CD16 and CD56 expression on CD4+ CD28 and CD8+ CD28 T cells are expressed as GMFI, which was determined by multicolor flow cytometry. Older adults were grouped as unimpaired (solid triangles) or impaired (open circles) based on a simple criterion of ADL = 0 and ADL > 1, respectively. Measurements of 3MS cognition score and gait speed and ADL scoring are as described in the text.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: NK-like T cells are linked to high cognitive and physical function. Data shown are 3D scatter plot summaries from the re-analyses of our data from the All Stars cohort of the Cardiovascular Health Study (70). CD16 and CD56 expression on CD4+ CD28 and CD8+ CD28 T cells are expressed as GMFI, which was determined by multicolor flow cytometry. Older adults were grouped as unimpaired (solid triangles) or impaired (open circles) based on a simple criterion of ADL = 0 and ADL > 1, respectively. Measurements of 3MS cognition score and gait speed and ADL scoring are as described in the text.
Mentions: Another way to illustrate the relationship between NK-like CD28 T cells and physical/cognitive functioning is shown in Figure 2 with a three dimensional plot for CD16 or CD56 expression levels (measured as GMFI, geometric mean fluorescence intensity), 3MS cognition score, and gait speed. The latter measure of physical function was determined by a 4-m walk test that has been standardized/validated from various cohort studies (16, 176). The data show a clear segregation between the high functioning and functionally impaired elders. This is surprising given that “impaired” and “unimpaired” categories in this graphical illustration are very loosely defined by ADL ≥ 1 and ADL = 0, respectively. Therefore, it will be of significant interest to determine if this three-way relationship between subsets of NK-like T cells, physical function, and cognitive ability translates into vigorous immune defense. In addition, the underlying mechanistic link(s) between these three physiologic systems will be instructive about integrative physiology 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.


Related in: MedlinePlus