CD8 T-cell immune phenotype of successful aging

Hui Chen Hsu; Donald K. Scott; Pili Zhang; Juling Zhou; Ping Ar Yang; Qi Wu; Harry W. Schroeder; Lynn B. Gerald; Eric Ravussin; S. Michal Jazwinski; John D. Mountz; Mark Batzer; Meghan Black; Evest A. Broussard; Laurie Byerley; Pauline Callinan; Katie E. Cherry; Yu Wen Chiu; Annie Cooper; James P. DeLany; W. Andrew Deutsch; Elizabeth T.H. Fontham; Madlyn Frisard; Paula Geiselman; Valentina Greco; Karri S. Hawley; Scott W. Herke; S. Michal Jazwinski; Darla Kendzor; Sangkyu Kim; Beth Kimball; Li Li; Kay Lopez; Yolanda Robertson; Henry Rothschild; Beth Schmidt; Donald K. Scott; F. Nicole Standberry; L. Joseph Su; Hui Yi Lin; Crystal P. Traylor; Robert H. Wood; Pili Zhang

doi:10.1016/j.mad.2005.10.001

CD8 T-cell immune phenotype of successful aging

Hui Chen Hsu, Donald K. Scott, Pili Zhang, Juling Zhou, Ping Ar Yang, Qi Wu, Harry W. Schroeder, Lynn B. Gerald, Eric Ravussin, S. Michal Jazwinski, John D. Mountz, Mark Batzer, Meghan Black, Evest A. Broussard, Laurie Byerley, Pauline Callinan, Katie E. Cherry, Yu Wen Chiu, Annie Cooper, James P. DeLanyW. Andrew Deutsch, Elizabeth T.H. Fontham, Madlyn Frisard, Paula Geiselman, Valentina Greco, Karri S. Hawley, Scott W. Herke, S. Michal Jazwinski, Darla Kendzor, Sangkyu Kim, Beth Kimball, Li Li, Kay Lopez, Yolanda Robertson, Henry Rothschild, Beth Schmidt, Donald K. Scott, F. Nicole Standberry, L. Joseph Su, Hui Yi Lin, Crystal P. Traylor, Robert H. Wood, Pili Zhang

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

The nonagenarian population by definition represents individuals who have demonstrated success in aging. We determined the status of CD8⁺ T-cell senescence in nonagenarians by analyzing the expression of CD28 and Fas (CD95), and analyzing activation and activation-induced cell death (AICD). Peripheral blood mononuclear cells (PBMCs) were isolated from three groups of subjects: adults (20-64-year-old), older adults (65-89-year-old), and nonagenarians (≥90-year-old). PBMCs were stimulated with phytohemagglutinin (PHA) (10 μg/ml). The cells were labeled with conjugated antibodies specific for CD4, CD8, CD28, CD45RO, and Fas, and were analyzed by FACS^®. There was a strong negative correlation of the percentage of CD28 ⁺Fas^- CD8⁺ T-cells with the age of each individual prior to stimulation in vitro (R² = 0.76, p < 0.0001). Compared to other biomarkers (CD28^-, CD28^-CD45RO ⁺, and Fas⁺) that have been associated with CD8 ⁺ T-cell aging, the loss of the CD28⁺Fas^- CD8⁺ T-cell population exhibited the strongest correlation with the individual's chronologic age. After stimulation with PHA, there was a decrease in the percentage of CD8⁺ T-cells from individual ≥65-year-old that expresses both CD28⁺ and Fas⁺ at day 3. Surprisingly, the AICD response of CD8⁺ T-cells at day 7 in the nonagenarians was higher than that in the other two groups. These results suggest that successful aging does not prevent development of the senescent phenotype of unstimulated CD8⁺ T cells, but is associated with preservation of CD8 T cell functions including activation and AICD. Increased AICD may result in enhanced rejuvenation capacity of T cells and limit the impact of aging on T cell function in nonagenarians.

Original language	English (US)
Pages (from-to)	231-239
Number of pages	9
Journal	Mechanisms of Ageing and Development
Volume	127
Issue number	3
DOIs	https://doi.org/10.1016/j.mad.2005.10.001
State	Published - Mar 1 2006
Externally published	Yes

Keywords

CD28
CD8 T-cells
Fas
Nonagenarians

ASJC Scopus subject areas

Aging
Developmental Biology

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10.1016/j.mad.2005.10.001

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Hsu, H. C., Scott, D. K., Zhang, P., Zhou, J., Yang, P. A., Wu, Q., Schroeder, H. W., Gerald, L. B., Ravussin, E., Jazwinski, S. M., Mountz, J. D., Batzer, M., Black, M., Broussard, E. A., Byerley, L., Callinan, P., Cherry, K. E., Chiu, Y. W., Cooper, A., ... Zhang, P. (2006). CD8 T-cell immune phenotype of successful aging. Mechanisms of Ageing and Development, 127(3), 231-239. https://doi.org/10.1016/j.mad.2005.10.001

Hsu, HC, Scott, DK, Zhang, P, Zhou, J, Yang, PA, Wu, Q, Schroeder, HW, Gerald, LB, Ravussin, E, Jazwinski, SM, Mountz, JD, Batzer, M, Black, M, Broussard, EA, Byerley, L, Callinan, P, Cherry, KE, Chiu, YW, Cooper, A, DeLany, JP, Deutsch, WA, Fontham, ETH, Frisard, M, Geiselman, P, Greco, V, Hawley, KS, Herke, SW, Jazwinski, SM, Kendzor, D, Kim, S, Kimball, B, Li, L, Lopez, K, Robertson, Y, Rothschild, H, Schmidt, B, Scott, DK, Standberry, FN, Su, LJ, Lin, HY, Traylor, CP, Wood, RH & Zhang, P 2006, 'CD8 T-cell immune phenotype of successful aging', Mechanisms of Ageing and Development, vol. 127, no. 3, pp. 231-239. https://doi.org/10.1016/j.mad.2005.10.001

@article{21955b6bf598402cacb8b17d0558e1a8,

title = "CD8 T-cell immune phenotype of successful aging",

abstract = "The nonagenarian population by definition represents individuals who have demonstrated success in aging. We determined the status of CD8+ T-cell senescence in nonagenarians by analyzing the expression of CD28 and Fas (CD95), and analyzing activation and activation-induced cell death (AICD). Peripheral blood mononuclear cells (PBMCs) were isolated from three groups of subjects: adults (20-64-year-old), older adults (65-89-year-old), and nonagenarians (≥90-year-old). PBMCs were stimulated with phytohemagglutinin (PHA) (10 μg/ml). The cells were labeled with conjugated antibodies specific for CD4, CD8, CD28, CD45RO, and Fas, and were analyzed by FACS{\textregistered}. There was a strong negative correlation of the percentage of CD28 +Fas- CD8+ T-cells with the age of each individual prior to stimulation in vitro (R2 = 0.76, p < 0.0001). Compared to other biomarkers (CD28-, CD28-CD45RO +, and Fas+) that have been associated with CD8 + T-cell aging, the loss of the CD28+Fas- CD8+ T-cell population exhibited the strongest correlation with the individual's chronologic age. After stimulation with PHA, there was a decrease in the percentage of CD8+ T-cells from individual ≥65-year-old that expresses both CD28+ and Fas+ at day 3. Surprisingly, the AICD response of CD8+ T-cells at day 7 in the nonagenarians was higher than that in the other two groups. These results suggest that successful aging does not prevent development of the senescent phenotype of unstimulated CD8+ T cells, but is associated with preservation of CD8 T cell functions including activation and AICD. Increased AICD may result in enhanced rejuvenation capacity of T cells and limit the impact of aging on T cell function in nonagenarians.",

keywords = "CD28, CD8 T-cells, Fas, Nonagenarians",

author = "Hsu, {Hui Chen} and Scott, {Donald K.} and Pili Zhang and Juling Zhou and Yang, {Ping Ar} and Qi Wu and Schroeder, {Harry W.} and Gerald, {Lynn B.} and Eric Ravussin and Jazwinski, {S. Michal} and Mountz, {John D.} and Mark Batzer and Meghan Black and Broussard, {Evest A.} and Laurie Byerley and Pauline Callinan and Cherry, {Katie E.} and Chiu, {Yu Wen} and Annie Cooper and DeLany, {James P.} and Deutsch, {W. Andrew} and Fontham, {Elizabeth T.H.} and Madlyn Frisard and Paula Geiselman and Valentina Greco and Hawley, {Karri S.} and Herke, {Scott W.} and Jazwinski, {S. Michal} and Darla Kendzor and Sangkyu Kim and Beth Kimball and Li Li and Kay Lopez and Yolanda Robertson and Henry Rothschild and Beth Schmidt and Scott, {Donald K.} and Standberry, {F. Nicole} and Su, {L. Joseph} and Lin, {Hui Yi} and Traylor, {Crystal P.} and Wood, {Robert H.} and Pili Zhang",

note = "Funding Information: This research was supported by a VA Merit Review Grant, by NIH/NIA RO1 AG11653 and NIH RR00032 (GCRC), and by the Louisiana Board of Regents through the Millennium Trust Health Excellence Fund [HEF(2001–06)-02]. We thank the Recruitment and Clinical Testing Core at the Pennington Biomedical Research Center for collecting the blood samples and the Sampling and Data Management Core at Louisiana State University Health Sciences Center for storage, quality control, and analyses of the data presented herein. We also acknowledge Ms. Enid Keyser and Ms. Tracey McGuire at the FACS {\textregistered} Core Facility at University of Alabama at Birmingham for operating the FACS {\textregistered} instrument, Ms. Jennifer Allen for expert proofread of the manuscript, and Ms. Carol Humber for excellent secretarial assistance.",

year = "2006",

month = mar,

day = "1",

doi = "10.1016/j.mad.2005.10.001",

language = "English (US)",

volume = "127",

pages = "231--239",

journal = "Mechanisms of Ageing and Development",

issn = "0047-6374",

publisher = "Elsevier Ireland Ltd",

number = "3",

}

TY - JOUR

T1 - CD8 T-cell immune phenotype of successful aging

AU - Hsu, Hui Chen

AU - Scott, Donald K.

AU - Zhang, Pili

AU - Zhou, Juling

AU - Yang, Ping Ar

AU - Wu, Qi

AU - Schroeder, Harry W.

AU - Gerald, Lynn B.

AU - Ravussin, Eric

AU - Jazwinski, S. Michal

AU - Mountz, John D.

AU - Batzer, Mark

AU - Black, Meghan

AU - Broussard, Evest A.

AU - Byerley, Laurie

AU - Callinan, Pauline

AU - Cherry, Katie E.

AU - Chiu, Yu Wen

AU - Cooper, Annie

AU - DeLany, James P.

AU - Deutsch, W. Andrew

AU - Fontham, Elizabeth T.H.

AU - Frisard, Madlyn

AU - Geiselman, Paula

AU - Greco, Valentina

AU - Hawley, Karri S.

AU - Herke, Scott W.

AU - Jazwinski, S. Michal

AU - Kendzor, Darla

AU - Kim, Sangkyu

AU - Kimball, Beth

AU - Li, Li

AU - Lopez, Kay

AU - Robertson, Yolanda

AU - Rothschild, Henry

AU - Schmidt, Beth

AU - Scott, Donald K.

AU - Standberry, F. Nicole

AU - Su, L. Joseph

AU - Lin, Hui Yi

AU - Traylor, Crystal P.

AU - Wood, Robert H.

AU - Zhang, Pili

N1 - Funding Information: This research was supported by a VA Merit Review Grant, by NIH/NIA RO1 AG11653 and NIH RR00032 (GCRC), and by the Louisiana Board of Regents through the Millennium Trust Health Excellence Fund [HEF(2001–06)-02]. We thank the Recruitment and Clinical Testing Core at the Pennington Biomedical Research Center for collecting the blood samples and the Sampling and Data Management Core at Louisiana State University Health Sciences Center for storage, quality control, and analyses of the data presented herein. We also acknowledge Ms. Enid Keyser and Ms. Tracey McGuire at the FACS ® Core Facility at University of Alabama at Birmingham for operating the FACS ® instrument, Ms. Jennifer Allen for expert proofread of the manuscript, and Ms. Carol Humber for excellent secretarial assistance.

PY - 2006/3/1

Y1 - 2006/3/1

N2 - The nonagenarian population by definition represents individuals who have demonstrated success in aging. We determined the status of CD8+ T-cell senescence in nonagenarians by analyzing the expression of CD28 and Fas (CD95), and analyzing activation and activation-induced cell death (AICD). Peripheral blood mononuclear cells (PBMCs) were isolated from three groups of subjects: adults (20-64-year-old), older adults (65-89-year-old), and nonagenarians (≥90-year-old). PBMCs were stimulated with phytohemagglutinin (PHA) (10 μg/ml). The cells were labeled with conjugated antibodies specific for CD4, CD8, CD28, CD45RO, and Fas, and were analyzed by FACS®. There was a strong negative correlation of the percentage of CD28 +Fas- CD8+ T-cells with the age of each individual prior to stimulation in vitro (R2 = 0.76, p < 0.0001). Compared to other biomarkers (CD28-, CD28-CD45RO +, and Fas+) that have been associated with CD8 + T-cell aging, the loss of the CD28+Fas- CD8+ T-cell population exhibited the strongest correlation with the individual's chronologic age. After stimulation with PHA, there was a decrease in the percentage of CD8+ T-cells from individual ≥65-year-old that expresses both CD28+ and Fas+ at day 3. Surprisingly, the AICD response of CD8+ T-cells at day 7 in the nonagenarians was higher than that in the other two groups. These results suggest that successful aging does not prevent development of the senescent phenotype of unstimulated CD8+ T cells, but is associated with preservation of CD8 T cell functions including activation and AICD. Increased AICD may result in enhanced rejuvenation capacity of T cells and limit the impact of aging on T cell function in nonagenarians.

AB - The nonagenarian population by definition represents individuals who have demonstrated success in aging. We determined the status of CD8+ T-cell senescence in nonagenarians by analyzing the expression of CD28 and Fas (CD95), and analyzing activation and activation-induced cell death (AICD). Peripheral blood mononuclear cells (PBMCs) were isolated from three groups of subjects: adults (20-64-year-old), older adults (65-89-year-old), and nonagenarians (≥90-year-old). PBMCs were stimulated with phytohemagglutinin (PHA) (10 μg/ml). The cells were labeled with conjugated antibodies specific for CD4, CD8, CD28, CD45RO, and Fas, and were analyzed by FACS®. There was a strong negative correlation of the percentage of CD28 +Fas- CD8+ T-cells with the age of each individual prior to stimulation in vitro (R2 = 0.76, p < 0.0001). Compared to other biomarkers (CD28-, CD28-CD45RO +, and Fas+) that have been associated with CD8 + T-cell aging, the loss of the CD28+Fas- CD8+ T-cell population exhibited the strongest correlation with the individual's chronologic age. After stimulation with PHA, there was a decrease in the percentage of CD8+ T-cells from individual ≥65-year-old that expresses both CD28+ and Fas+ at day 3. Surprisingly, the AICD response of CD8+ T-cells at day 7 in the nonagenarians was higher than that in the other two groups. These results suggest that successful aging does not prevent development of the senescent phenotype of unstimulated CD8+ T cells, but is associated with preservation of CD8 T cell functions including activation and AICD. Increased AICD may result in enhanced rejuvenation capacity of T cells and limit the impact of aging on T cell function in nonagenarians.

KW - CD28

KW - CD8 T-cells

KW - Fas

KW - Nonagenarians

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JO - Mechanisms of Ageing and Development

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IS - 3

ER -

CD8 T-cell immune phenotype of successful aging

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Keywords

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