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Age-dependent alterations of the T cell repertoire and functional diversity of T cells of the aged

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Abstract

The aging immune system is characterized by the contraction of T cell receptor (TCR) diversity and the de novo expression of NK-related receptors (NKR) on oligoclonal T cells. NKR+T cells likely represent a secondary immune diversification as a biological adaptation of aging to ensure host defense despite shrinkage of the TCR repertoire. NKRs are expressed in various combinations even among TCR-identical cells, and are capable of triggering effector pathways in either TCR-independent or TCR-dependent fashion. Understanding the biology of NKR+ T cells will be pivotal to the development of strategies to enhance immunity in the elderly.

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References

  1. Nikolich-Zugich J, Slifka MK, Messaoudi I: The many important facets of T-cell repertoire diversity. Nat Rev Immunol 2004; 4:123–132.

    Article  PubMed  CAS  Google Scholar 

  2. Naylor K, Li G, Vallejo AN, et al: The influence of age on T cell generation and TCR diversity. J Immunol 2005; 174:7446–7452.

    PubMed  CAS  Google Scholar 

  3. Guimond M, Fry TJ, Mackall CL: Cytokine signals in T-cell homeostasis. J Immunother 2005; 28:289–294.

    Article  PubMed  CAS  Google Scholar 

  4. Fagnoni FF, Vescovini R, Passeri G, et al: Shortage of circulating naive CD8(+) T cells provides new insights on immunodeficiency in aging. Blood. 2000; 95:2860–2868.

    PubMed  CAS  Google Scholar 

  5. Wack A, Cossarizza A, Heltai S, et al: Age-related modification of the human alphabeta T cell repertoire due to different clonal expansions in the CD4+ and CD8+ subsets. Int Immunol 1998; 10:1281–1288.

    Article  PubMed  CAS  Google Scholar 

  6. Hulstaert F, Hannet I, Deneys V, et al: Age-related changes in human blood lymphocyte subpopulations. II. Varying kinetics of percentage and absolute count measurements. Clin Immunol Immunopathol 1994; 70: 152–158.

    Article  PubMed  CAS  Google Scholar 

  7. Posnett DN, Sinha R, Kabak S, et al: Clonal populations of T cells in normal elderly humans: the T cell equivalent to “benign monoclonal gammapathy”. J Exp Med 1994; 179:609–618.

    Article  PubMed  CAS  Google Scholar 

  8. Simonsen L, Reichert TA, Viboud C, et al: Impact of influenza vaccination on seasonal mortality in the US elderly population. Arch Intern Med 2005; 165:265–272.

    Article  PubMed  Google Scholar 

  9. Reichert TA, Sugaya N, Fedson DS, et al: The Japanese experience with vaccinating schoolchildren against influenza. N Engl J Med 2001; 344:889–896.

    Article  PubMed  CAS  Google Scholar 

  10. Ghendon YZ, Kaira AN, Elshina GA: The effect of mass influenza immunization in children on the morbidity of the unvaccinated elderly. Epidemiol Infect 2006; 134:71–78.

    Article  PubMed  CAS  Google Scholar 

  11. Maynard J, Petersson K, Wilson DH, et al: Structure of an autoimmune T cell receptor complexed with class II peptide-MHC: insights into MHC bias and antigen specificity. Immunity 2005; 22:81–92.

    PubMed  CAS  Google Scholar 

  12. Hadrup SR, Strindhall J, Kollgaard T, et al: 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 2006; 176:2645–2653.

    PubMed  CAS  Google Scholar 

  13. Sadighi Akha AA, Miller RA: Signal transduction in the aging immune system. Curr Opin Immunol 2005; 17:486–491.

    Article  PubMed  CAS  Google Scholar 

  14. Swain S, Clise-Dwyer K, Haynes L. Homeostasis and the age-associated defect of CD4 T cells. Semin Immunol 2005; 17:370–377.

    Article  PubMed  CAS  Google Scholar 

  15. Khan N, Hislop A, Gudgeon N, et al: Herpesvirus-specific CD8 T cell immunity in old age: cytomegalovirus impairs the response to a coresident EBV infection. J Immunol 2004; 173:7481–7489.

    PubMed  CAS  Google Scholar 

  16. Messaoudi I, Lemaoult J, Guevara-Patino JA, et al: Age-related CD8T cell clonal expansions constrict CD8 T cell repertoire and have the potential to impair immune defense. J Exp Med 2004; 200:1347–1358.

    Article  PubMed  CAS  Google Scholar 

  17. Son NH, Murray S, Yanovski J, et al: Lineage-specific telomere shortening and unaltered capacity for telomerase expression in human T and B lymphocytes with age. J Immunol 2000; 165:1191–1196.

    PubMed  CAS  Google Scholar 

  18. Shay JW, Wright WE: Hayflick, his limit, and cellular ageing. Nat Rev Mol Cell Biol 2000; 1:72–76.

    Article  PubMed  CAS  Google Scholar 

  19. Satyanarayana A, Wiemann SU, Buer J, et al: Telomere shortening impairs organ regeneration by inhibiting cell cyclere-entry of a subpopulation of cells. EMBO J 2003; 22:4003–4013.

    Article  PubMed  CAS  Google Scholar 

  20. Wright WE, Shay JW: Telomere dynamics in cancer progression and prevention: fundamental differences in human and mouse telomere biology. Nat Med 2000; 6:849–851.

    Article  PubMed  CAS  Google Scholar 

  21. Stoltzner G, Makinodan T: Age dependent decline in proliferation of lymphocytes. Adv Exp Med Biol 1975; 61:21–37.

    PubMed  CAS  Google Scholar 

  22. Effros RB, Dagarag M, Spaulding C, et al: The role of CD8+ T-cell replicative senescence in human aging. Immunol Rev 2005; 205:147–157.

    Article  PubMed  CAS  Google Scholar 

  23. Abedin S, Michel JJ, Lemster B, et al: Diversity of NKR expression in aging T cells and in T cells of the aged: the new frontier into the exploration of protective immunity in the elderly. Exp Gerontol 2005; 40:537–548.

    Article  PubMed  CAS  Google Scholar 

  24. Campisi J: Cancer, aging and cellular senescence. In Vivo 2000; 14:183–188.

    PubMed  CAS  Google Scholar 

  25. Vallejo AN: CD28 extinction in human T cells: altered functions and the program of T-cell senescence. Immunol Rev 2005; 205:158–169.

    Article  PubMed  CAS  Google Scholar 

  26. Vallejo AN, Weyand CM, Goronzy JJ: Functional disruption of the CD28 transcriptional initiator in senescent T cells. J Biol Chem 2001; 276:2565–2570.

    Article  PubMed  CAS  Google Scholar 

  27. Lewis DE, Merched-Sauvage M, Goronzy JJ, et al: Tumor necrosis factor-alpha and CD80 modulate CD28 expression through a similar mechanism of T-cell receptor-independent inhibition of transcription. J Biol Chem 2004; 279:29130–29138.

    Article  PubMed  CAS  Google Scholar 

  28. Bruunsgaard H: Effects of tumor necrosis factor-alpha and interleukin-6 in elderly populations. Eur Cytokine Netw 2002; 13:389–391.

    PubMed  CAS  Google Scholar 

  29. Vallejo AN, Nestel AR, Schirmer M, et al: Aging-related deficiency of CD28 expression in CD4+ T cells is associated with the loss of gene-specific nuclear factor binding activity. J Biol Chem 1998; 273:8119–8129.

    Article  PubMed  CAS  Google Scholar 

  30. Monteiro J, Batliwalla F, Ostrer H, et al: Shortened telomeres in clonally expanded CD28− CD8+ T cells imply a replicative history that is distinct from their CD28+CD8+ counterparts. J Immunol 1996; 156:3587–3590.

    PubMed  CAS  Google Scholar 

  31. Scheuring UJ, Sabzevari H, Theofilopoulos AN: Proliferative arrest and cell cycle regulation in CD8(+)CD28(−) versus CD8(+)CD28(+) T cells. Hum Immunol 2002; 63:1000–1009.

    Article  PubMed  CAS  Google Scholar 

  32. Linn YC, Hui KM: Cytokine-induced killer cells: NK-like T cells with cytotolytic specificity against leukemia. Leuk Lymphoma 2003; 44:1457–1462.

    Article  PubMed  CAS  Google Scholar 

  33. Bratke K, Kuepper M, Bade B, et al: Differential expression of human granzymes A, B, and K in natural killer cells and during CD8+ T cell differentiation in peripheral blood. Eur J Immunol 2005; 35:2608–2616.

    Article  PubMed  CAS  Google Scholar 

  34. Voehringer D, Koschella M, Pircherh H: Lack of proliferative capacity of human effector and memory T cells expressing killer cell lectinlike receptor G1 (KLRG1). Blood 2002; 100:3698–3702.

    Article  PubMed  CAS  Google Scholar 

  35. Gonzalez S, Groh V, Spies T: Immunobiology of human NKG2D and its ligands. Curr Top Microbiol Immunol 2006; 298:121–138.

    Article  PubMed  CAS  Google Scholar 

  36. Moretta L, Moretta A: Killer immunoglobulin-like receptors. Curr Opin Immunol 2004; 16:626–633.

    Article  PubMed  CAS  Google Scholar 

  37. Snyder MR, Muegge LO, Offord C, et al: Formation of the killer Ig-like receptor repertoire on CD4+CD28null T cells. J Immunol 2002; 168:3839–3846.

    PubMed  CAS  Google Scholar 

  38. Vely F, Peyrat M, Couedel C, et al: Regulation of inhibitory and activating killer-cell Ig-like receptor expression occurs in T cells after termination of TCR rearrangements. J Immunol 2001; 166:2487–2494.

    PubMed  CAS  Google Scholar 

  39. van Bergen J, Thompson A, van der Slik A, et al: Phenotypic and functional characterization of CD4 T cells expressing killer Ig-like receptors. J Immunol 2004; 173:6719–6726.

    PubMed  Google Scholar 

  40. Xu J, Vallejo AN, Jiang Y, et al: Distinct transcriptional control mechanisms of killer immunoglobulin-like receptors in natural killer (NK) and in T cells. J Biol Chem 2005; 280:24277–24285.

    Article  PubMed  CAS  Google Scholar 

  41. Snyder MR, Weyand CM, Goronzy JJ: The double life of NK receptors: stimulation or costimulation? Trends Immunol 2004; 25:25–32.

    Article  PubMed  CAS  Google Scholar 

  42. Anfossi N, Doisne JM, Peyrat MA, et al: Coordinated expression of Ig-like inhibitory MHC class I receptors and acquisition of cytotoxic function in human CD8+ T cells. J Immunol 2004; 173:7223–7229.

    PubMed  CAS  Google Scholar 

  43. van Leeuwen EM, Remmerswaal EB, Vossen MT, et al: Emergence of a CD4+CD28− granzyme B+, cytomegalovirus-specific T cell subset after recovery of primary cytomegalovirus infection. J Immunol 2004; 173:1834–1841.

    PubMed  Google Scholar 

  44. Kikuchi-Maki A, Yusa S, Catina TL, et al: KIR2DL4 is an IL-2-regulated NK cell receptor that exhibits limited expression in humans but triggers strong IFN-gamma production. J Immunol 2003; 171:3415–3425.

    PubMed  CAS  Google Scholar 

  45. Dorothee G, Echchakir H, Le Maux Chansac B, et al: Functional and molecular characterization of a KIR3DL2/p 140 expressing tumor-specific cytotoxic T lymphocyte clone infiltrating a human lung carcinoma. Oncogene 2003; 22:7192–7198.

    Article  PubMed  CAS  Google Scholar 

  46. Boyington JC, Brooks AG, Sun PD: Structure of killer cell immunoglobulin-like receptors and their recognition of the class I MHC molecules. Immunol Rev 2001; 181:66–78.

    Article  PubMed  CAS  Google Scholar 

  47. Becker S, Tonn T, Fussel T, et al: Assessment of killer cell immunoglobulinlike receptor expression and corresponding HLA class I phenotypes demonstrates heterogenous KIR expression independent of anticipated HLA class I ligands. Hum Immunol 2003; 64:183–193.

    Article  PubMed  CAS  Google Scholar 

  48. Katz G, Gazit R, Arnon TI, et al: MHC class I-independent recognition of NK-activating receptor KIR2DS4. J Immunol 2004; 173:1819–1825.

    PubMed  CAS  Google Scholar 

  49. Boyson JE, Erskine R, Whitman MC, et al: Disulfide bond-mediated dimerization of HLA-G on the cell surface. Proc Natl Acad Sci USA 2002; 99: 16180–16185.

    Article  PubMed  CAS  Google Scholar 

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Author notes

  1. Abbe N. Vallejo PhD

    Present address: Division of Rheumatology, Children's Hospital of Pittsburgh Rangos, Research Center, 3460 Fifth Avenue, 15213, Pittsburgh, PA

Authors and Affiliations

  1. Departments of Pediatrics and Immunology, University of Pittsburgh School of Medicine, 15213, Pittsburgh, PA

    Abbe N. Vallejo PhD

  2. the Mniversity of Pittsburgh Cancer Institute, 15213, Pittsburgh, PA

    Abbe N. Vallejo PhD

  3. the McGowan Institute for Regenerative Medicine, 15213, Pittsburgh, PA

    Abbe N. Vallejo PhD

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Vallejo, A.N. Age-dependent alterations of the T cell repertoire and functional diversity of T cells of the aged. Immunol Res 36, 221–228 (2006). https://doi.org/10.1385/IR:36:1:221

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