Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 627K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Messaoudi, I. Articles by Nikolich-Zugich, J. Search for Related Content PubMed PubMed Citation Articles by Messaoudi, I. Articles by Nikolich-Zugich, J. Pubmed/NCBI databases Medline Plus Health Information Seniors' Health Social Bookmarking                      What's this?

Ilhem Messaoudi, Joël LeMaoult, Jose A. Guevara-Patino, Beatrix M. Metzner, and Janko Nikolich-ugich

Vaccine and Gene Therapy Institute and the Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006

Address correspondence to Janko Nikolich-ugich, Vaccine and Gene Therapy Institute, Oregon Health & Science University, West Campus, 505 NW 185th Ave., Beaverton, OR 97006. Phone: (503) 418-2752; Fax: (503) 418-2764; email: nikolich{at}ohsu.edu

Peripheral T cell diversity is virtually constant in the young, but is invariably reduced in aged mice and humans. CD8⁺ T cell clonal expansions (TCE) are the most drastic manifestation of, and possible contributors to, this reduced diversity. We show that the presence of TCE results in reduced CD8⁺, but not CD4⁺, T cell diversity, and in functional inability to mobilize parts of the CD8⁺ T cell repertoire affected by TCE. In the model of herpes simplex virus (HSV)-1 infection of B6 mice, >90% of the responding CD8⁺ T cells use Vß10 or Vß8 and are directed against a single glycoprotein B (gB_498-505) epitope, gB-8p. We found that old animals bearing CD8⁺ TCE within Vß10 or Vß8 families failed to mount an effective immune response against HSV-1, as judged by reduced numbers of peptide-major histocompatibility complex tetramer⁺ CD8 T cells and an absence of antiviral lytic function. Furthermore, Vß8 TCE experimentally introduced into young mice resulted in lower resistance to viral challenge, whereas Vß5⁺ TCE induced in a similar fashion did not impact viral resistance. These results demonstrate that age-related TCE functionally impair the efficacy of antiviral CD8⁺ T cell immunity in an antigen-specific manner, strongly suggesting that TCE are not the mere manifestation of, but are also a contributing factor to, the immunodeficiency of senescence.

Key Words: aging • TCR • T cell clonal expansions • repertoire diversity • antiviral immunity

J.A. Guevara-Patino's present address is Dept. of Surgery, Pritzker Medical School, University of Chicago, 924 E. 57th Ave., Chicago, IL 60637.

B.M. Metzner's present address is Medigene, Inc., Lochhamer Str. 11, 85152 Martinsried, Germany.

Abbreviations used in this paper: ATX, adult thymectomy; CTLp, TEL precursors; FCM, flow cytofluorometry; pMHC, peptide-MHC; TCE, T cell clonal expansion(s).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Ahmed, M., Lanzer, K. G., Yager, E. J., Adams, P. S., Johnson, L. L., Blackman, M. A. (2009). Clonal Expansions and Loss of Receptor Diversity in the Naive CD8 T Cell Repertoire of Aged Mice. J. Immunol. 182: 784-792 [Abstract] [Full Text]  
• Clambey, E. T., White, J., Kappler, J. W., Marrack, P. (2008). Identification of two major types of age-associated CD8 clonal expansions with highly divergent properties. Proc. Natl. Acad. Sci. USA 105: 12997-13002 [Abstract] [Full Text]  
• Lin, S.-J., Chen, A. T., Welsh, R. M. (2008). Immune system derived from homeostatic proliferation generates normal CD8 T-cell memory but altered repertoires and diminished heterologous immune responses. Blood 112: 680-689 [Abstract] [Full Text]  
• Parsons, R., Lelic, A., Hayes, L., Carter, A., Marshall, L., Evelegh, C., Drebot, M., Andonova, M., McMurtrey, C., Hildebrand, W., Loeb, M. B., Bramson, J. L. (2008). The Memory T Cell Response to West Nile Virus in Symptomatic Humans following Natural Infection Is Not Influenced by Age and Is Dominated by a Restricted Set of CD8+ T Cell Epitopes. J. Immunol. 181: 1563-1572 [Abstract] [Full Text]  
• Voehringer, D., Liang, H.-E., Locksley, R. M. (2008). Homeostasis and Effector Function of Lymphopenia-Induced "Memory-Like" T Cells in Constitutively T Cell-Depleted Mice. J. Immunol. 180: 4742-4753 [Abstract] [Full Text]  
• Yager, E. J., Ahmed, M., Lanzer, K., Randall, T. D., Woodland, D. L., Blackman, M. A. (2008). Age-associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virus. JEM 205: 711-723 [Abstract] [Full Text]  
• Cicin-Sain, L., Messaoudi, I., Park, B., Currier, N., Planer, S., Fischer, M., Tackitt, S., Nikolich-Zugich, D., Legasse, A., Axthelm, M. K., Picker, L. J., Mori, M., Nikolich-Zugich, J. (2007). Dramatic increase in naive T cell turnover is linked to loss of naive T cells from old primates. Proc. Natl. Acad. Sci. USA 104: 19960-19965 [Abstract] [Full Text]  
• Ely, K. H., Ahmed, M., Kohlmeier, J. E., Roberts, A. D., Wittmer, S. T., Blackman, M. A., Woodland, D. L. (2007). Antigen-Specific CD8+ T Cell Clonal Expansions Develop from Memory T Cell Pools Established by Acute Respiratory Virus Infections. J. Immunol. 179: 3535-3542 [Abstract] [Full Text]  
• Pourgheysari, B., Khan, N., Best, D., Bruton, R., Nayak, L., Moss, P. A. H. (2007). The Cytomegalovirus-Specific CD4+ T-Cell Response Expands with Age and Markedly Alters the CD4+ T-Cell Repertoire. J. Virol. 81: 7759-7765 [Abstract] [Full Text]  
• Akbar, A. N., Vukmanovic-Stejic, M. (2007). Telomerase in T Lymphocytes: Use It and Lose It?. J. Immunol. 178: 6689-6694 [Abstract] [Full Text]  
• Messaoudi, I., Warner, J., Fischer, M., Park, B., Hill, B., Mattison, J., Lane, M. A., Roth, G. S., Ingram, D. K., Picker, L. J., Douek, D. C., Mori, M., Nikolich-Zugich, J. (2006). From the Cover: Delay of T cell senescence by caloric restriction in aged long-lived nonhuman primates. Proc. Natl. Acad. Sci. USA 103: 19448-19453 [Abstract] [Full Text]  
• Messaoudi, I., Warner, J., Nikolich-Zugich, J. (2006). Age-Related CD8+ T Cell Clonal Expansions Express Elevated Levels of CD122 and CD127 and Display Defects in Perceiving Homeostatic Signals.. J. Immunol. 177: 2784-2792 [Abstract] [Full Text]  
• Matsumoto, Y., Matsuo, H., Sakuma, H., Park, I.-K., Tsukada, Y., Kohyama, K., Kondo, T., Kotorii, S., Shibuya, N. (2006). CDR3 Spectratyping Analysis of the TCR Repertoire in Myasthenia Gravis.. J. Immunol. 176: 5100-5107 [Abstract] [Full Text]  
• Kim, H.-R., Hong, M. S., Dan, J. M., Kang, I. (2006). Altered IL-7R{alpha} expression with aging and the potential implications of IL-7 therapy on CD8+ T-cell immune responses. Blood 107: 2855-2862 [Abstract] [Full Text]  
• Hadrup, S. R., Strindhall, J., Kollgaard, T., Seremet, T., Johansson, B., Pawelec, G., thor Straten, P., Wikby, A. (2006). Longitudinal Studies of Clonally Expanded CD8 T Cells Reveal a Repertoire Shrinkage Predicting Mortality and an Increased Number of Dysfunctional Cytomegalovirus-Specific T Cells in the Very Elderly. J. Immunol. 176: 2645-2653 [Abstract] [Full Text]  
• Messaoudi, I., Warner, J., Nikolich-Zugich, D., Fischer, M., Nikolich-Zugich, J. (2006). Molecular, Cellular, and Antigen Requirements for Development of Age-Associated T Cell Clonal Expansions In Vivo. J. Immunol. 176: 301-308 [Abstract] [Full Text]  
• Fletcher, J. M., Vukmanovic-Stejic, M., Dunne, P. J., Birch, K. E., Cook, J. E., Jackson, S. E., Salmon, M., Rustin, M. H., Akbar, A. N. (2005). Cytomegalovirus-Specific CD4+ T Cells in Healthy Carriers Are Continuously Driven to Replicative Exhaustion. J. Immunol. 175: 8218-8225 [Abstract] [Full Text]  
• Roberts, A. D., Ely, K. H., Woodland, D. L. (2005). Differential contributions of central and effector memory T cells to recall responses. JEM 202: 123-133 [Abstract] [Full Text]  
• Posnett, D. N., Engelhorn, M. E., Houghton, A. N. (2005). Antiviral T cell responses: phalanx or multipronged attack?. JEM 201: 1881-1884 [Abstract] [Full Text]  
• Nikolich-Zugich, J. (2005). T cell aging: naive but not young. JEM 201: 837-840 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS