| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Department of Medicine, Mayo Clinic and Graduate School, Rochester, MN 55905; Department of Medicine, Emory University School of Medicine, Kathleen B. and Mason I. Lowance Center for Human Immunology, Atlanta, GA 30322
The ability to mount protective immune responses depends on the diversity of T cells. T cell diversity may be compromised by the declining thymic output of new T cells. The aging process imposes a threat to diversity, because thymic function deteriorates. In this study we have examined the relationship between thymic production, homeostatic T cell proliferation and TCR 
-chain diversity in young (
25 years), middle-aged (60 years), and elderly adults (75 years). TCR excision circles (TREC) as a marker of thymic output exponentially decreased by >95% between 25 and 60 years of age. The frequency of Ki67+ cycling CD4 T cells remained steady, and surprisingly, the diversity of the naive CD4 T cell repertoire was maintained at 2 x 107 different TCR -chains. After the age of 70 years, TRECs only slightly declined, but homeostatic proliferation doubled. The diversity of the T cell pool drastically contracted to 200,000 TCR -chains. Also, the phenotypic distinction between naive and memory CD4 T cells became fuzzy. The collapse in CD4 T cell diversity during the seventh and eighth decades indicates substantial T cell loss and implies that therapeutic measures to improve vaccine responses will have to include strategies for T cell replenishment.
Related articles in The JI:
This article has been cited by other articles:
|
|
 |
|
  H. S. Robins, P. V. Campregher, S. K. Srivastava, A. Wacher, C. J. Turtle, O. Kahsai, S. R. Riddell, E. H. Warren, and C. S. Carlson Comprehensive assessment of T-cell receptor {beta}-chain diversity in {alpha}{beta} T cells Blood, November 5, 2009; 114(19): 4099 - 4107. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Boding, C. M. Bonefeld, B. L. Nielsen, J. P. H. Lauritsen, M. R. von Essen, A. K. Hansen, J. M. Larsen, M. M. Nielsen, N. Odum, and C. Geisler TCR Down-Regulation Controls T Cell Homeostasis J. Immunol., October 15, 2009; 183(8): 4994 - 5005. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Li, M. Yu, C. M. Weyand, and J. J. Goronzy Epigenetic regulation of killer immunoglobulin-like receptor expression in T cells Blood, October 15, 2009; 114(16): 3422 - 3430. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yang, Y.-H. Youm, and V. D. Dixit Inhibition of Thymic Adipogenesis by Caloric Restriction Is Coupled with Reduction in Age-Related Thymic Involution J. Immunol., September 1, 2009; 183(5): 3040 - 3052. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A R Lorenzi, T A Morgan, A Anderson, J Catterall, A M Patterson, H E Foster, and J D Isaacs Thymic function in juvenile idiopathic arthritis Ann Rheum Dis, June 1, 2009; 68(6): 983 - 990. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kohler and A. Thiel Life after the thymus: CD31+ and CD31- human naive CD4+ T-cell subsets Blood, January 22, 2009; 113(4): 769 - 774. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ahmed, K. G. Lanzer, E. J. Yager, P. S. Adams, L. L. Johnson, and M. A. Blackman Clonal Expansions and Loss of Receptor Diversity in the Naive CD8 T Cell Repertoire of Aged Mice J. Immunol., January 15, 2009; 182(2): 784 - 792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. E. Jenkinson, A. Bacon, A. J. White, G. Anderson, and E. J. Jenkinson An Epithelial Progenitor Pool Regulates Thymus Growth J. Immunol., November 1, 2008; 181(9): 6101 - 6108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Huang, D. J. Moore, R. J. Ketchum, C. S. Nunemaker, B. Kovatchev, A. L. McCall, and K. L. Brayman Resolving the Conundrum of Islet Transplantation by Linking Metabolic Dysregulation, Inflammation, and Immune Regulation Endocr. Rev., August 1, 2008; 29(5): 603 - 630. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Voehringer, H.-E. Liang, and R. M. Locksley Homeostasis and Effector Function of Lymphopenia-Induced "Memory-Like" T Cells in Constitutively T Cell-Depleted Mice J. Immunol., April 1, 2008; 180(7): 4742 - 4753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lang, J. D. Brien, I. Messaoudi, and J. Nikolich-Zugich Age-Related Dysregulation of CD8+ T Cell Memory Specific for a Persistent Virus Is Independent of Viral Replication J. Immunol., April 1, 2008; 180(7): 4848 - 4857. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Yager, M. Ahmed, K. Lanzer, T. D. Randall, D. L. Woodland, and M. A. Blackman Age-associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virus J. Exp. Med., March 17, 2008; 205(3): 711 - 723. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Sutherland, L. Spyroglou, J. L. Muirhead, T. S. Heng, A. Prieto-Hinojosa, H. M. Prince, A. P. Chidgey, A. P. Schwarer, and R. L. Boyd Enhanced Immune System Regeneration in Humans Following Allogeneic or Autologous Hemopoietic Stem Cell Transplantation by Temporary Sex Steroid Blockade Clin. Cancer Res., February 15, 2008; 14(4): 1138 - 1149. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Kilpatrick, T. Rickabaugh, L. E. Hultin, P. Hultin, M. A. Hausner, R. Detels, J. Phair, and B. D. Jamieson Homeostasis of the Naive CD4+ T Cell Compartment during Aging J. Immunol., February 1, 2008; 180(3): 1499 - 1507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. H. Lemster, J. J. Michel, D. T. Montag, J. J. Paat, S. A. Studenski, A. B. Newman, and A. N. Vallejo Induction of CD56 and TCR-Independent Activation of T Cells with Aging J. Immunol., February 1, 2008; 180(3): 1979 - 1990. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Castermans, F. Baron, E. Willems, N. Schaaf-Lafontaine, N. Meuris, A. Gothot, J.-F. Vanbellighen, C. Herens, L. Seidel, V. Geenen, et al. Evidence for neo-generation of T cells by the thymus after non-myeloablative conditioning Haematologica, February 1, 2008; 93(2): 240 - 247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yang, P. K. Epling-Burnette, J. S. Painter, J. Zou, F. Bai, S. Wei, and T. P. Loughran Jr Antigen activation and impaired Fas-induced death-inducing signaling complex formation in T-large-granular lymphocyte leukemia Blood, February 1, 2008; 111(3): 1610 - 1616. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R.-H. Voss, R. A. Willemsen, J. Kuball, M. Grabowski, R. Engel, R. S. Intan, P. Guillaume, P. Romero, C. Huber, and M. Theobald Molecular Design of the C{alpha} Interface Favors Specific Pairing of Introduced TCR{alpha} in Human T Cells J. Immunol., January 1, 2008; 180(1): 391 - 401. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Cicin-Sain, I. Messaoudi, B. Park, N. Currier, S. Planer, M. Fischer, S. Tackitt, D. Nikolich-Zugich, A. Legasse, M. K. Axthelm, et al. Dramatic increase in naive T cell turnover is linked to loss of naive T cells from old primates PNAS, December 11, 2007; 104(50): 19960 - 19965. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Kochenderfer, J. L. Simpson, C. D. Chien, and R. E. Gress Vaccination regimens incorporating CpG-containing oligodeoxynucleotides and IL-2 generate antigen-specific antitumor immunity from T-cell populations undergoing homeostatic peripheral expansion after BMT Blood, July 1, 2007; 110(1): 450 - 460. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Sumpter, R. Dunham, S. Gordon, J. Engram, M. Hennessy, A. Kinter, M. Paiardini, B. Cervasi, N. Klatt, H. McClure, et al. Correlates of Preserved CD4+ T Cell Homeostasis during Natural, Nonpathogenic Simian Immunodeficiency Virus Infection of Sooty Mangabeys: Implications for AIDS Pathogenesis J. Immunol., February 1, 2007; 178(3): 1680 - 1691. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Witkowski, M. Soroczynska-Cybula, E. Bryl, Z. Smolenska, and A. Jozwik Klotho--a Common Link in Physiological and Rheumatoid Arthritis-Related Aging of Human CD4+ Lymphocytes J. Immunol., January 15, 2007; 178(2): 771 - 777. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Messaoudi, J. Warner, M. Fischer, B. Park, B. Hill, J. Mattison, M. A. Lane, G. S. Roth, D. K. Ingram, L. J. Picker, et al. From the Cover: Delay of T cell senescence by caloric restriction in aged long-lived nonhuman primates PNAS, December 19, 2006; 103(51): 19448 - 19453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. van den Dool and R. J. de Boer The Effects of Age, Thymectomy, and HIV Infection on {alpha} and beta TCR Excision Circles in Naive T Cells J. Immunol., October 1, 2006; 177(7): 4391 - 4401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Hadrup, J. Strindhall, T. Kollgaard, T. Seremet, B. Johansson, G. Pawelec, P. thor Straten, and A. Wikby 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., February 15, 2006; 176(4): 2645 - 2653. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Grabar, L. Weiss, and D. Costagliola HIV infection in older patients in the HAART era J. Antimicrob. Chemother., January 1, 2006; 57(1): 4 - 7. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Messaoudi, J. Warner, D. Nikolich-Zugich, M. Fischer, and J. Nikolich-Zugich Molecular, Cellular, and Antigen Requirements for Development of Age-Associated T Cell Clonal Expansions In Vivo J. Immunol., January 1, 2006; 176(1): 301 - 308. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
