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The Journal of Immunology, 2002, 169: 1984-1992.
Copyright © 2002 by The American Association of Immunologists

Cytomegalovirus Seropositivity Drives the CD8 T Cell Repertoire Toward Greater Clonality in Healthy Elderly Individuals1

Naeem Khan*, Naseer Shariff{dagger}, Mark Cobbold*, Rachel Bruton*, Jenni A. Ainsworth*, Alan J. Sinclair{dagger}, Laxman Nayak{dagger} and Paul A. H. Moss2,*

* Cancer Research U.K. Institute for Cancer Studies and {dagger} Department of Geriatric Medicine, University of Birmingham, Edgbaston, United Kingdom

The deterioration in immune function with aging is thought to make a major contribution to the increased morbidity and mortality from infectious disease in old age. One aspect of immune senescence is the reduction in CD8 T cell repertoire as due to the accumulation of oligoclonal, memory T cells and a reduction in the naive T cell pool. CD8 T cell clonal expansions accumulate with age, but their antigenic specificity remains unknown. In this study, we show that in elderly individuals seropositivity for human CMV leads to the development of oligoclonal populations of CMV-specific CTL that can constitute up to one-quarter of the total CD8 T cell population. Furthermore, CMV-specific CTL have a highly polarized membrane phenotype that is typical of effector memory cells (CD28-, CD57+, CCR7-). TCR analyses show that CMV-specific CTL have highly restricted clonality with greater restriction in the larger expansions. Clonal analysis of the total CD8 T cell repertoire was compared between CMV-seropositive and CMV-seronegative donors. Thirty-three percent more clonal expansions were observed in CMV-seropositive donors in comparison with seronegative individuals. These data implicate CMV as a major factor in driving oligoclonal expansions in old age. Such a dramatic accumulation of virus-specific effector CTL might impair the ability to respond to heterologous infection and may underlie the negative influence of CMV seropositivity on survival in the very elderly.




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Y. Deng, Y. Jing, A. E. Campbell, and S. Gravenstein
Age-Related Impaired Type 1 T Cell Responses to Influenza: Reduced Activation Ex Vivo, Decreased Expansion in CTL Culture In Vitro, and Blunted Response to Influenza Vaccination In Vivo in the Elderly
J. Immunol., March 15, 2004; 172(6): 3437 - 3446.
[Abstract] [Full Text] [PDF]

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D. D. Sloan, G. Zahariadis, C. M. Posavad, N. T. Pate, S. J. Kussick, and K. R. Jerome
CTL Are Inactivated by Herpes Simplex Virus-Infected Cells Expressing a Viral Protein Kinase
J. Immunol., December 15, 2003; 171(12): 6733 - 6741.
[Abstract] [Full Text] [PDF]

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J. E. Bower, P. A. Ganz, N. Aziz, J. L. Fahey, and S. W. Cole
T-Cell Homeostasis in Breast Cancer Survivors With Persistent Fatigue
J Natl Cancer Inst, August 6, 2003; 95(15): 1165 - 1168.
[Abstract] [Full Text] [PDF]

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R. J. Davenport
Immunity Challenge
Sci. Aging Knowl. Environ., June 11, 2003; 2003(23): oa1 - 1.
[Abstract] [Full Text] [PDF]

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U. Karrer, S. Sierro, M. Wagner, A. Oxenius, H. Hengel, U. H. Koszinowski, R. E. Phillips, and P. Klenerman
Memory Inflation: Continuous Accumulation of Antiviral CD8+ T Cells Over Time
J. Immunol., February 15, 2003; 170(4): 2022 - 2029.
[Abstract] [Full Text] [PDF]

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V. Prod'homme, C. Retiere, B.-M. Imbert-Marcille, M. Bonneville, and M.-M. Hallet
Modulation of HLA-A*0201-Restricted T Cell Responses by Natural Polymorphism in the IE1315-324 Epitope of Human Cytomegalovirus
J. Immunol., February 15, 2003; 170(4): 2030 - 2036.
[Abstract] [Full Text] [PDF]


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