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Characteristics of the Immunoresponse in Elderly People and Autoimmunity

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Abstract

Aging is a highly complex process that results in the dysregulation of all systems in the human organism. The most important changes in the immune system, which are collectively known as immunosenescence, include lower levels of immunoresponse to infections, increased levels of proinflammatory mediators, and weakened control over self-reactive clones. In elderly people, immunoscenescence is usually observed along with low-grade, aseptic inflammation (inflammaging) which is considered to be associated with a higher incidence of chronic, noninfectious, age-related diseases. This paper discusses the main changes in the innate and adaptive immunity in aging and their impact on the induction of autoimmune processes and provides data on the frequency of autoantibody detection in elderly people and the clinical patterns of certain autoimmune diseases that manifest first at this age.

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REFERENCES

  1. Blinova, E.A., Zinnatova, E.V., Barkovskaya, M.S., et al., Telomere length of individual chromosomes in patients with rheumatoid arthritis, Bull. Exp. Biol. Med., 2016, vol. 160, no. 6, pp. 779–782.

    Article  CAS  PubMed  Google Scholar 

  2. Agrawal, A., Agrawal, S., Cao, J.N., et al., Altered innate immune functioning of dendritic cells in elderly humans: a role of phosphoinositide 3-kinase-signaling pathway, J. Immunol., 2007, vol. 178, no. 11, pp. 6912–6922.

    Article  CAS  PubMed  Google Scholar 

  3. Agrawal, A., Tay, J., Ton, S., et al., Increased reactivity of dendritic cells from aged subjects to self-antigens, J. Immunol., 2009, vol. 182, no. 2, pp. 1138–1145.

    Article  CAS  PubMed  Google Scholar 

  4. Aljohami, R., Gladman, D.D., Su, J., and Urowitz, M.B., Disease evolution in late-onset and early-onset systemic lupus erythematosus, Lupus, 2017, vol. 26, no. 11, pp. 1190–1196.

    Article  Google Scholar 

  5. Almeida-Olivera, A., Smith-Carvalho, M., Porto, L.C., et al., Age-related changes in natural killer receptors from childhood through old age, Hum. Immunol., 2011, vol. 72, no. 3, pp. 319–329.

    Article  CAS  Google Scholar 

  6. Alonso-Arias, R., Moro-García, M.A., López-Vázquez, A., et al., NKG2D expression in CD 4+ T lymphocytes as a marker of senescence in the aged system, Age (Dordrecht), 2011, vol. 33, no. 4, pp. 591–605.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Andersen-Ranberg, K., Hǿier-Madasten, M., Wilk, A., et al., High prevalence of autoantibodies among Danish centenarians, Clin. Exp. Immunol., 2004, vol. 138, no. 1, pp. 158–163.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Bayersdorf, R., Fruscalzo, A., and Catania, F., Linking autoimmunity to the origin of the adaptive immune system, Evol. Med. Publ. Health, 2018, vol. 1, pp. 2–12.

    Article  Google Scholar 

  9. Blair, P.A., Noreńa, L.Y., Flores-Borja, F., et al., CD 19+CD24(hi)CD38(hi) B cells exhibit regulatory capacity in health individuals but are functionally impaired on systemic lupus erythematosus patients, Immunity, 2010, vol. 32, no. 2, pp. 129–140.

    Article  CAS  PubMed  Google Scholar 

  10. Borrego, F., Alonso, M.C., Galiani, M.D., et al., NK phenotypic markers and IL2 response in NK cells from elderly people, Gerontology, 1999, vol. 34, no. 2, pp. 253–265.

    CAS  Google Scholar 

  11. Chanouzas, D., Sagmeister, M., Faustni, S., et al., Subclinical reactivation of cytomegalovirus drives CD4+CD28null N-cell expansion and impaired immune response to pneumococcal vaccination in antineutrophil cytoplasmic antibody-associated vasculitis, J. Infect. Dis., 2019, vol. 2019, no. 2, pp. 234–244.

    Article  CAS  Google Scholar 

  12. Childrawar, S.M., Khan, N., Chan, Y.L.T., et al., Aging is associated with a decline in peripheral blood CD56 bright NK cells, Immun. Aging, 2006, vol. 23, art. 10. https://doi.org/10.1186/1742-4933-3-10

  13. Chiu, B.C., Martin, B.E., Stolberg, V.R., and Chensue, S.W., The host environment is responsible for aging-related functional NK cell deficiency, J. Immunol., 2013, vol. 191, no. 9, pp. 4688–4698.

    Article  CAS  PubMed  Google Scholar 

  14. Claes, N., Fraussen, J., Vanheusden, M., et al., Age-associated B cell with proinflammatory characteristics are expanded in a proportion in multiple sclerosis patients, J. Immunol., 2016, vol. 197, no. 12, pp. 4576–4583.

    Article  CAS  PubMed  Google Scholar 

  15. Coder, B., Wang, H., Ruan, L., and Su, D.M., Thymic involution pertubs negative selection leading to autoreactive T cells that induce chronic inflammation, J. Immunol., 2015, vol. 194, no. 12, pp. 5825–5837.

    Article  CAS  PubMed  Google Scholar 

  16. De la Fuente, M. and Miquel, J., An update of the oxidation-inflammation theory of aging: the involvement of the immune system in oxi-inflamm-aging, Curr. Pharm. Des., 2009, vol. 15, no. 26, pp. 3003–3026.

    Article  CAS  PubMed  Google Scholar 

  17. Martínez de Toda, I., Vida, C., San Miguel, S.L., and De la Fuente, M., Function, oxidative and inflammatory stress parameters in immune cells as predictive markers of lifespan throughout aging, Oxid. Med. Cell. Longevity, 2019, vol. 2019, art. ID 4574276. https://doi.org/10.1155/2019/4574276

  18. Den Braber, I., Mugwaga, T., Vrisekoop, N., et al., Maintenance of peripheral naive T cells is sustained by thymus output in mice but not humans, Immunity, 2012, vol. 36, no. 2, pp. 288–297.

    Article  CAS  PubMed  Google Scholar 

  19. Dimri, G.P., Lee, X., Basile, G., et al., A biomarker that identify es senescent human cells in culture and in aging skin in vivo, Proc. Natl. Acad. Sci. U.S.A., 1995, vol. 92, no. 20, pp. 9363–9367.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Duggal, N.A., Upton, J., Phillips, A.C., et al., An age-related numerical and functional deficit in CD19+CD24hiCD38hi B cells is associated with an increase in systemic autoimmunity, Aging Cell, 2013, vol. 12, no. 5, pp. 873–881.

    Article  CAS  PubMed  Google Scholar 

  21. Ellis, J.C. and Braley-Mullen, H., Mechanisms by which B cells and regulatory T cells influence development of murine organ-specific autoimmune diseases, J. Clin. Med., 2017, vol. 6, no. 2, p. 13. https://doi.org/10.3390/jcm6020013

    Article  CAS  PubMed Central  Google Scholar 

  22. Fagnoni, F.F., Vescovini, R., Mazzola, M., et al., Expansion of cytotoxic CD8+CD28– T cells in healthy aging people, including centenarians, Immunology, 1996, vol. 88, no. 4, pp. 501–507.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Fessler, J., Raicht, A., Husic, R., et al., Novel senescent regulatory T-cell subset with impaired suppressive function in rheumatoid arthritis, Front. Imunol., 2017, vol. 8, p. 300. https://doi.org/10.3389/fimmu.2017.00300

    Article  CAS  Google Scholar 

  24. Frasca, D., Diaz, A., Romero, M., and Blomberg, B.B., Human peripheral late/exhausted memory B cells express a senescent-associated secretory phenotype and preferentially utilize metabolic signaling pathways, Exp. Gerontol., 2017, vol. 87, part A, pp. 113– 120. https://doi.org/10.1016/j.exger.2016.12.001

    Article  CAS  PubMed  Google Scholar 

  25. Gajic-Veljic, M., Bonaci-Nikolic, B., Lekic, B., et al., Importance of low serum DNase I activity and polyspecific anti-neutrophil cytoplasmic antibodies in propylthiouracil-induced lupus-like syndrome, Rheumatology (Oxford), 2015, vol. 54, no. 11, pp. 2061–2070.

    Article  CAS  PubMed  Google Scholar 

  26. Gardner, J.K., Cornwall, S.M.J., Musk, A.W., et al., Elderly dendritic cells respond to LPS/IFN and CD40L stimulation despite incomplete maturation, PLoS One, 2018, vol. 13, no. 4, p. e0195313. https://doi.org/10.1371/journal.pone.0195313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Garretti, F., Agalliu, D., Lindestam Arlehamn, C.S., et al., Autoimmunity in Parkinson’s disease: the role of α-synuclein-specific T-cells, Front. Immunol., 2019, vol. 10, p. 303. https://doi.org/10.3389/fimmu.2019.00303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Holder, A., Mirczuk, S.M., Fowkes, R., et al., Perturbation of the T cell receptor repertoire occurs with increasing age in dogs, Dev. Comp. Immunol., 2018, vol. 79, pp. 150–157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Jackson, S.W., Scharping, N.E., Kolhatkar, N.S., et al., Opposing impact of B cell-intrinsic TLR7 and TLR9 signals on autoantibody repertoire and system inflammation, J. Immunol., 2014, vol. 192, no. 10, pp. 4525–4532.

    Article  CAS  PubMed  Google Scholar 

  30. Jagger, A., Shimojima, Y., Goronzy, J.J., and Weyand, C.M., Regulatory T-cells and the immune aging process: a mini-review, Gerontology, 2014, vol. 60, no. 2, pp. 130–137.

    Article  CAS  PubMed  Google Scholar 

  31. Johnson, S.A., Rozzo, S.J., and Cambier, J.C., Aging-dependent exclusion of antigen-inexperienced cells from the peripheral B cell repertoire, J. Immunol., 2002, vol. 168, no. 10, pp. 5014–5023.

    Article  CAS  PubMed  Google Scholar 

  32. Jurk, D., Wilson, C., Passos, J.F., et al., Chronic inflammation induces telomere dysfunction and accelerates aging in mice, Nat. Commun., 2014, vol. 2, p. 4172. https://doi.org/10.1038/ncomms5172

    Article  CAS  PubMed  Google Scholar 

  33. Ishjigaki, K., Shoda, H., Kochi, Y., et al., Quantitative and qualitative characterization of expanded CD4+ T cell clones in rheumatoid arthritis patients, Sci. Rep., 2015, vol. 5, p. 12937. https://doi.org/10.1038/srep12937

    Article  CAS  Google Scholar 

  34. Kerstein, A., Schüler, S., Cabral-Marques, O., et al., Environmental factor and inflammation-driven alteration of the total peripheral T-cell compartment in granulematosis with polyangiitis, J. Autoimmunol., 2017, vol. 78, pp. 79–91.

    Article  CAS  Google Scholar 

  35. Khandpur, R., Carmona-Rivera, C., Vivekanandan-Giri, A., et al., NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis, Sci. Transl. Med., 2013, vol. 5, no. 178, art. ID 178ra40. https://doi.org/10.1126/scitranslmed.3005580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. King, C., Ilic, A., Koelsch, K., and Sarvetnic, N., Homeostatic expansion of T cell during immune insufficiency generates autoimmunity, Cell, 2004, vol. 117, no. 2, pp. 265–277.

    Article  CAS  PubMed  Google Scholar 

  37. Lefebvre, J.S., Maue, A.C., Eaton, S.M., et al., The aged microenvironment contributes to the age-related functional defects of CD4 T cells in mice, Aging Cell, 2012, vol. 11, no. 5, pp. 732–740.

    Article  CAS  PubMed  Google Scholar 

  38. Le Garff-Tavernier, M., Bėziat, V., Decocq, J., et al., Human NK cells display major phenotypic and functional changes over the life, Aging Cell, 2010, vol. 9, no. 4, pp. 527–535.

    Article  CAS  PubMed  Google Scholar 

  39. Le Page, A., Dupius, G., Larbi, A., et al., Signal transduction changes in CD4+ and CD8+ T-cell subpopulations with aging, Exp. Gerontol., 2018, vol. 125, pp. 128–139.

    Article  CAS  Google Scholar 

  40. Li, X., Ding, D., Yao, J., et al., Chromatin remodeling factor BAZ1A regulates cellular senescence in both cancer and normal cells, Life Sci., 2019, vol. 229, pp. 225–232.

    Article  CAS  PubMed  Google Scholar 

  41. Lilliebladh, S., Johansson, A., Petterson, A., et al., Phenotypic characterization of circulating CD4+ T cells in ANCA associated vasculitis, J. Immunol. Res., 2018, vol. 2018, art. ID 6984563. https://doi.org/10.1155/2018/6984563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Lindau, P., Mukherjee, R., Gutschow, M.V., et al., Cytomegalovirus exposure in the elderly does not reduce CD8 T-cell repertoire diversity, J. Immunol., 2019, vol. 202, no. 2, pp. 476–483.

    Article  CAS  PubMed  Google Scholar 

  43. Liu, Y., Seto, N.L., Carmona-Rivera, C., and Kaplan, M.G., Accelerated model of lupus autoimmunity and vasculopathy driven by Toll-like receptor 7/9 imbalance, Lupus Sci. Med., 2018, vol. 5, no. 1, p. e000259. https://doi.org/10.1136/lupus-2018-000259

    Article  PubMed  PubMed Central  Google Scholar 

  44. Martens, P.B., Goronzy, J.J., Schaid, D., and Weyand, C.M., Expansion of unusual CD4+ T cells in severe rheumatoid arthritis, Arthritis Rheumatol., 1997, vol. 40, no. 6, pp. 1106–1114.

    Article  CAS  Google Scholar 

  45. Nagele, E.P., Han, M., Acharya, N.K., et al., Natural IgG autoantibodies are abundant and ubiquitous in human sera, and their number is influenced by age, gender and disease, PLoS One, 2013, vol. 8, p. e60726. https://doi.org/10.1371/journal.pone.0060726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Oliviery, F., Rippo, M.R., Monsurró, V., et al., MicroRNAs-linking inflamm-aging, cellular senescence and cancer, Ageing Res. Rev., 2013, vol. 12, no. 4, pp. 1056–1068.

    Article  CAS  Google Scholar 

  47. Panda, A., Qian, F., Mohanty, S., et al., Age-associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response, J. Immunol., 2010, vol. 184, no. 5, pp. 2518–2527.

    Article  CAS  PubMed  Google Scholar 

  48. Petersen, L.E., Schuch, J.B., De Azeredo, L., et al., Characterization of senescence biomarkers in rheumatoid arthritis: relevance to disease progression, Clin. Rheumatol., 2019, vol. 38, no. 10, pp. 2909–2915.

    Article  PubMed  Google Scholar 

  49. Pievan, A., Borleri, G., Pende, D., et al., Dual-function capability of CD 3+CD 56+ CIK cells, a T-cell subset that acquires NK function and retains TCR-mediated specific cytotoxicity, Blood, 2011, vol. 118, no. 12, pp. 3301–3310.

    Article  CAS  Google Scholar 

  50. Qin, L., Jing, X., Qiu, Z., et al., Aging of immune system: immune signature from peripheral blood lymphocyte subset in 1068 healthy adults, Aging (Albany, NY), 2016, vol. 8, no. 5, pp. 848–859.

    Article  CAS  Google Scholar 

  51. Ribon, M., Seninet, S., Mussard, J., et al., Neutrophil extracellular traps exert both pro- and anti-inflammatory actions in rheumatoid arthritis that are modulated by C1q and LL-37, J. Autoimmunol., 2019, vol. 98, pp. 122–131.

    Article  CAS  Google Scholar 

  52. Rosato, E. and Salsano, F., Immunity, autoimmunity and autoimmune diseases in older people, J. Biol. Regul. Agents, 2008, vol. 22, no. 4, pp. 217–224.

    CAS  Google Scholar 

  53. Rubtsov, A.V., Rubtsova, K., Fischer, A., et al., Toll-like receptor 7 (TLR7)-driven accumulation of a novel CD11c B-cell population is important for the development of autoimmunity, Blood, 2011, vol. 118, no. 5, pp. 1305–1315.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Rubtsova, K., Rubtsov, A.V., Cancro, M.P., and Marrack, P., Age-associated B cells: a T-bet-dependent effector with roles in protective and pathogenic immunity, J. Immunol., 2015, vol. 195, no. 5, pp. 1933–1937.

    Article  CAS  PubMed  Google Scholar 

  55. Rudd, P.D., Ventyri, V., Davenport, M.P., and Nikolich-Zugich, J., Evolution of the antigen-specific CD8+ TCR repertoire across the lifespan: evidence for clonal homogenization of the old TCR repertoire, J. Immunol., 2011, vol. 186, no. 4, pp. 2056–2064.

    Article  CAS  PubMed  Google Scholar 

  56. Ruffatti, A., Rossi, L., Calligaro, A., et al., Autoantibodies of systemic rheumatic diseases in the healthy elderly, Gerontology, 1990, vol. 36, no. 2, pp. 104–111.

    Article  CAS  PubMed  Google Scholar 

  57. Sato, K., Kato, A., Sekai, M., et al., Physiologic thymic involution underlies age-dependent accumulation of senescence-associated CD4+ T cells, J. Immunol., 2017, vol., 199, no. 1, pp. 138–148.

  58. Sauce, D., Larsen, M., Fastenackels, S., et al., Lymphopeniadriven homeostatic regulation of naive T cells in elderly and thymectomized young adults, J. Immunol., 2012, vol. 189, no. 12, pp. 5541–5548.

    Article  CAS  PubMed  Google Scholar 

  59. Schehata, H.M., Hoebe, K., and Chougnet, C.A., The aged nonhematopoetic environment impairs natural killer cell maturation and function, Aging Cell, 2015, vol. 14, no. 2, pp. 191–199.

    Article  CAS  Google Scholar 

  60. Schmitt, V., Rink, L., and Uciechowski, P., The Th17/Treg balance is disturbed during aging, Exp. Gerontol., 2013, vol. 48, no. 12, pp. 1379–1386.

    Article  CAS  PubMed  Google Scholar 

  61. Shodell, M. and Siegal, F.P., Circulating interferon-producing plasmacytoid dendritic cells decline during human aging, Scand. J. Immunol., 2002, vol. 56, no. 5, pp. 518–521.

    Article  CAS  PubMed  Google Scholar 

  62. Tahir, S., Fukushima, Y., Sakamoto, K., et al., A CD153+ CD4+ T follicular cell population with cell-senescence features plays a critical role in lupus pathogenesis via osteopontin production, J. Immunol., 2015, vol. 194, no. 12, pp. 5725–5735.

    Article  CAS  PubMed  Google Scholar 

  63. Tan, T.C., Gao, X., Thong, B.Y., et al., Comparison of elderly- and young-onset rheumatoid arthritis in Asian cohort, Int. J. Rheumatol. Dis., 2017, vol. 20, no. 6, pp. 737–745.

    Article  CAS  Google Scholar 

  64. Thewessen, M., Somers, V., Hellings, N., et al., CD4+CD28null T cells in autoimmune disease: pathogenic features and decreased susceptibility to immunoregulation, J. Immunol., 2007, vol. 179, no. 10, pp. 6514–6523.

    Article  Google Scholar 

  65. Vida, C., Martínez de Toda, I., Cruces, J., et al., Role of macrophages in age-related oxidative stress and accumulation in mice, Redox Biol., 2017, vol. 12, pp. 423–437.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Wang, J., Yang, G., Wang, D., et al., Changes of peripheral lymphocyte subsets and cytokine environment during aging and deterioration gastrointestinal tract status, Oncotarget, 2017, vol. 8, no. 37, pp. 60764–60777. https://doi.org/10.18632/oncotarget.18485

    Article  PubMed  PubMed Central  Google Scholar 

  67. Watad, A., Bragazzi, N.C., Adawi, M., et al., Autoimmunity in the elderly: insights from basic science and clinics—a mini-review, Gerontology, 2017, vol. 63, no. 6, pp. 515–523.

    Article  CAS  PubMed  Google Scholar 

  68. Wu, J. and Ling, L., Autoantibodies in Alzheimer’s disease: potential biomarkers, pathogenic roles, and therapeutic implication, J. Biomed. Res., 2016, vol. 30, no. 5, pp. 361–372.

    PubMed  PubMed Central  Google Scholar 

  69. Xu, F., Zhang, C., Zou, Z., et al., Aging-related Atg5 defect impairs neutrophil extracellular traps formation, Immunology, 2017, vol. 151, no. 4, pp. 417–432.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Yang, G., Wu, D., Zeng, G., et al., Correlation between miR-126 expression and DNA hypomethylation of CD4+ T cells in rheumatoid arthritis patients, Int. J. Clin. Exp. Pathol., 2015, vol. 8, no. 8, pp. 8929–8936.

    PubMed  PubMed Central  Google Scholar 

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    O. V. Moskalec

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Moskalec, O.V. Characteristics of the Immunoresponse in Elderly People and Autoimmunity. Adv Gerontol 10, 368–376 (2020). https://doi.org/10.1134/S2079057020040153

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