Skip to main content
SpringerLink
Log in

The immune S ystem in the elderly

II. Specific Cellular Immunity

  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

Numerous changes occur in the immune system with advancing age, probably contributing to the decreased immunoresponsiveness in the elderly. These changes are often associated with important clinical manifestations such as increased susceptibility to infection and cancer frequently observed in the elderly population. Although both cellular and humoral immune responses are modified with advancing age, much of the decrease in immunoresponsiveness seen in elderly populations is associated with changes in T cell responses. The loss of effective immune activity is largely due to alterations within the T cell compartment which occur, in part, as a result of thymic involution. Substantial changes in both the functional and phenotypic profiles of T cells have been reported with advancing age. In fact, two prominent features of immunosenescence are altered T cell phenotype and reduced T cell response. One of the most consistent changes noted in T cells with advancing age is the decrease in the proportion of naive T cells with a concomitant increase in T cells with an activated/memory phenotype. In addition, there is evidence that the T cell population from aged individuals is hyporesponsive. The observed functional changes include decreased responsiveness to T cell receptor stimulation, impaired T cell proliferative capacity, a decline in the frequency of CD4+ T cells producing IL-2 and a decreased expression in IL2 receptors. These latter findings probably explain the loss of proliferative capability of T cells from aged individuals. There is also evidence of a decrease in the early events of signal transduction, decreased activationinduced intracellular phosphorylation, and decreased cellular proliferatice response to T cell receptor stimulation. The present review analyzes the main changes of the T cell compartment characterizing immunosenescence and discusses the possible mechanisms underlying these disregulations and their clinical implications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Patel HR. Miller RA: Age-associated changes in mitogen-induced protein phosphorylation in murine T lymphocytes. Eur. J. Immunol. 1992;22:253–260.

    Article  PubMed  CAS  Google Scholar 

  2. Ernst DN, Weigle WO, Noonan DJ, McQuitty DN, Hobbs MV: The ageassociated increase in IFN-γsynthesis by mouse CD8+ T cells correlates with shifts in the frequencies of cell subsets defined by membrane CD44, CD45RB, 3G11, andMEL-14expression J. Immunol. 1993;151:575–587.

    PubMed  CAS  Google Scholar 

  3. Engwerda CR, Handwerger BS, Fox BS: Aged T cells are hyporesponsive to costimulation mediated by CD28. J. Immunol. 1994; 152:3740–3747.

    PubMed  CAS  Google Scholar 

  4. Linton PJ, Haynes L, Klinman NR. Swain S: Antigen-independent changes in naive CD4 T cells with aging. J. Exp. Med. 1996;184:1891–1900.

    Article  PubMed  CAS  Google Scholar 

  5. Brosche T, Platt D: Nutritional factors and age-associated changes in cellular immunity and phagocytosis: amini-review. Aging Immunol. Infect. Dis. 1995;6:31–42.

    Google Scholar 

  6. Quaglino D, Ginaldi L, Furia N, De Martinis M: The effect of age on hemopoiesis. Aging Clin. Exp. Res. 1996;8:1–12.

    CAS  Google Scholar 

  7. Bender BS, Nagel JE, Adler WH, Andres R: Absolute peripheral blood lymphocyte count and subsequent mortality of elderly men. J. Am. Geriatr. Soc. 1986;24:649–654.

    Google Scholar 

  8. Flurkey K, Stadecker M, Miller RA: Memory T lymphocyte hyporesponsiveness to non-cognate stimuli: a key factor in age-related immunodeficiency. Eur. J. Immunol. 1992;22: 931–935.

    Article  PubMed  CAS  Google Scholar 

  9. Kirschman DA, Murasko DM: Splenic and inguinal lymph node T cells of aged mice respond differently to polyclonal and antigen-specific stimuli. Cell. Immunol. 1992; 139:426–437.

    Article  Google Scholar 

  10. Shi J, Miller RA: Differential tyrosine-specific protein phosphorylation in mouse T lymphocyte subsets: effect of age. J. Immunol. 1993;151:730–739.

    PubMed  CAS  Google Scholar 

  11. Tanchot C, Rocha B: The peripheral T cell repertoire: independent homeostatic regulation of virgin and activated CD8+ T cell pools. Eur. J. Immunol. 1995;25:2127–2136.

    Article  PubMed  CAS  Google Scholar 

  12. Pahlavani MA, Richardson A: The effect of age on the expression of interleukin-2. Mech. Ageing Dev. 1996;89:125–154.

    Article  CAS  Google Scholar 

  13. Rea IM. Stewart M, Campbell P, Alexander HD, Crockard AD, Morris TCM: Changes in lymphocyte subsets, interleukin 2, and soluble interleukin 2 receptor in old and very old age. Gerontology 1996;42:69–78.

    PubMed  CAS  Google Scholar 

  14. Riancho JA, Zarrabeitia MT, Amado JA, Olmos JM, Gonzalez-Macias J: Age-related differences in cytokine secretion. Gerontology 1994;40:8–12.

    Article  PubMed  CAS  Google Scholar 

  15. Frasca D, Pucci S, Goso C, Barattini P, Barile S, Pioli C, Doria G: Regulation of cytokine production in aging: use of recombinant cytokines to upregulate mitogen-stimulated spleen cells. Mech. Ageing Dev. 1997;93:157–169.

    Article  PubMed  CAS  Google Scholar 

  16. Shearer GM: Th1/Th2 changes in aging. Mech. Ageing Dev. 1997;94:1–5.

    Article  CAS  Google Scholar 

  17. Engwerda CR, Handwerger BS, Fox BS: Aged T cells are hyporesponsive to co-stimulation mediated by CD28. J. Immunol. 1994; 52:3740–3747.

    Google Scholar 

  18. Powers DC, Manning MC, Morley JE, Flood JF: Age-related changes in lymphoproliferation, cytotoxic T lymphocyte responses, and natural killer activity of senescence-accelerated mouse (SAM)-P/8 and SAMR/1 substrains. Aging Immunol. Infect. Dis. 1995;643-52.

  19. Hirokawa K, Utsuyama M, Kasai M, Jurachima C, Ishijima S, Zeng YX: Understanding the machanism of the age-related change of thymic function to promote T cell differentiation. Immunol. Lett. 1994;40:269–277.

    Article  PubMed  CAS  Google Scholar 

  20. Thoman ML: Early steps in T cell development are affected by aging. Cell. Immunol. 1997; 178:117–123.

    Article  PubMed  CAS  Google Scholar 

  21. Thoman ML:Effects of the aged microenvironment on CD4+ T cell maturation. Mech. Ageing Dev. 1997;96:75–88.

    Article  PubMed  CAS  Google Scholar 

  22. Lee W, Yin XM, Vitetta E: Functional and ontogenetic analysis of murine CD45Rhi and CD45Rlo CD4+ T cells. J. Immunol. 1990; 144:3288–3295.

    PubMed  CAS  Google Scholar 

  23. Utsuyama M, Hirokawa K, Jurashima C: Differential age-change in the numbers of CD4+CD45RA+ and CD4+CD29+ T cell subsets in human peripheral blood. Mech. Ageing Dev. 1992;63:57–68.

    Article  PubMed  CAS  Google Scholar 

  24. Cossarizza A, Ortolani C, Paganelli R: Age-related imbalance of virgin (CD45RA+) and memory (CD45RO+) cells between CD4+ and CD8+ T lymphocytes in humans: a study from newborns to centenarians. J. Immunol. Res. 1992;4:118–126.

    Google Scholar 

  25. Franceschi C, Monti D, Sansoni P, Cossarizza A.: The immunology of exceptional individuals: the lesson of centenarians. Immunol. Today 1995;16:12–16.

    Article  PubMed  CAS  Google Scholar 

  26. Scolley R, Butcher E, Weissman I: Thymus cell migration. Quantitative aspects of cellular traffic from the thymus to the periphery in mice. Eur. J. Immunol. 1980;10:210–218.

    Article  Google Scholar 

  27. Sansoni P, Cossarizza A, Brianti V, Fagnoni F, Snelli G, Monti D, et al.: Lymphocyte subsets and natural killer cell activity in healthy old people and centenarians. Blood 1993;80:2767–2773.

    Google Scholar 

  28. Cossarizza A, Ortolani C, Monti D, Franceschi C: Cytometric analysis of immunosenescence. Cytometry 1997;27:297–313.

    Article  PubMed  CAS  Google Scholar 

  29. Miller RA: The cell biology of aging: immunological models. J. Gerontol. 1989;44:B4-B8.

    PubMed  CAS  Google Scholar 

  30. Jackola DR, Ruger JK, Miller RA: Age-associated changes in human T cell phenotype and function. Aging Clin. Exp. Res. 1994;6:25–34.

    CAS  Google Scholar 

  31. Liu J, Wang S, Liu H, Yang L, Nan G: The monitoring biomarker for immune function of lymphocytes in the elderly. Mech. Ageing Dev. 1997;94:177–182.

    Article  PubMed  CAS  Google Scholar 

  32. Akbar AN, Terry L, Beverley PCL, Janossy G: Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells. J. Immunol. 1988;140:2171–2178.

    PubMed  CAS  Google Scholar 

  33. Cerottini JC, MacDonald HR: The cellular basis of T-cell memory. Annu. Rev. Immunol. 1989;7:77–89.

    Article  PubMed  CAS  Google Scholar 

  34. Cossarizza A, Ortolani C, Paganelli R, Barbieri D, Monti D, Sansoni P, et al: CD45 isoforms expression on CD4+ and CD8+ T cells throughout life, from newborns to centenarians: implications for T cell memory. Mech. Ageing Dev. 1996;86:173–195.

    Article  PubMed  CAS  Google Scholar 

  35. Linton PJ, Haynes L, Tsui L, Zhang X, Swain S: From naive to effector alterations with aging. Immunol. Rev. 1997;160:9–18.

    Article  PubMed  CAS  Google Scholar 

  36. Bradley LM, Duncan DD, Yoshimoto K, Swain SL: Memory effectors: a potent, IL-4 secreting helper T cell population that develops after restimulation with antigen. J. Immunol. 1993;150:3119–3130.

    PubMed  CAS  Google Scholar 

  37. Swain SL, Bradley LM, Croft M, Dubey C, Haynes L, Rogers P, Zhang X, Bradley LM: From naive to memory T cells. Immunol. Rev. 1996;150:143–167.

    Article  PubMed  CAS  Google Scholar 

  38. Lerner A, Yamada T, Miller RA: Pgp-1hi T lymphocytes accumulate with age in mice and respond poorly to concanavalin A. Eur. J. Immunol. 1989;19:977–982.

    Article  PubMed  CAS  Google Scholar 

  39. Miller RA, Garcia G, Kirk CJ, Witkowski J.M.: Early activation defects in T lymphocytes from aged mice. Immunol. Rev. 1997; 160:79–90.

    Article  PubMed  CAS  Google Scholar 

  40. Garcia GG, Miller RA: Differential tyrosine phosphorylation of zeta chain dimers in mouse CD4 T lymphocytes: effect of age. Cell. Immunol. 1997;175:51–57.

    Article  PubMed  CAS  Google Scholar 

  41. Negoro S, Hara H, Miyata S, Saiki O, Tanaka T, Yoshizaki K, Igarashi T, Kishimoto S: Mechanisms of age-related decline in antigen-specific T cell proliferative response: IL-2 receptor expression and recombinant IL-2 induced proliferative response of purified TAC-positive T cells. Mech. Ageing Dev. 1986;36:223–241.

    Article  PubMed  CAS  Google Scholar 

  42. Cossarizza A, Kahan M, Ortolani C, Franceschi C, Londei M: Preferential expression of Vb6.7 domain on human peripheral CD4+ T cells. Implications for posistive selection of T cells in man. Eur. J. Immunol. 1991;21:1571–1574.

    Article  PubMed  CAS  Google Scholar 

  43. Bradley LM, Bradley IS, King DL, Shiigi SM: Predominance of T cells that express CD45R in the CD4+ helper/inducer lymphocyte subset of neonates. Clin. Immunol. Immunopathol. 198951:426–435.

    Article  PubMed  CAS  Google Scholar 

  44. Hajward AR, Lee I, Beverley PCL: Ontogeny of expression of UCHL1 antigen on TCR-1+ (CD4/8) and TCRd+ T cells. Eur. J. Immunol. 1989;19:771–773.

    Article  Google Scholar 

  45. De Paoli S, Battistini S, Santini GF: Age-related changes in human lymphocyte subsets:progressive reduction of the CD4 CD45R (suppressor inducer) population. Clin. Immunol. Immunopathol. 1988; 48:290–296.

    Article  PubMed  Google Scholar 

  46. Gonzalez-Quintial R, Theophilopoulos AN: V beta gene repertoires in aging mice. J. Immunol. 1992; 149:230–236.

    PubMed  CAS  Google Scholar 

  47. Callahan IE, Kappler JW, Marrack P: Unexpected expansions of CD8bearing cells in old mice. J. Immunol. 1993;151:6657–6669.

    PubMed  CAS  Google Scholar 

  48. Posnett DN, Sinha R, Kabak S, Russo C: Clonal population of T cell in normal elderly humans: the T cell equivalent to “benign monoclonal gammopathy”. J. Exp. Med. 1994;179:609–618.

    Article  PubMed  CAS  Google Scholar 

  49. Cossarizza A, Barbieri D, Londei M: T cell repertoire usage in humans, from newborns to centenarians. Int. Rev. Immunol. 1995;12:41–45.

    Article  PubMed  CAS  Google Scholar 

  50. Schwab R, Szabo P, Manavalan I, Weksler ME, Posnett DN, Pannetier C, Kourilsky P, Even J: Expanded CD4+ and CD8+ T cell clones in elderly humans. J. Immunol. 1997; 158:4493–4499.

    PubMed  CAS  Google Scholar 

  51. Mackall CL, Gress RE: Thymic aging and T cell regeneration. Immunol. Rev. 1997;160:91–102.

    Article  PubMed  CAS  Google Scholar 

  52. Fink PJ, Matis LA, McElligott DL, Bookman M, Hedrick SM: Correlations between T-cell specificity and the structure of the antigen receptor. Nature 1986;321:219–226.

    Article  PubMed  CAS  Google Scholar 

  53. Kimura N, Toyonaga B, Yoshikai Y, Du RP, Mak TW: Sequences and repertoire of the human T cell receptor alpha and beta chain variable genes in thymocytes. Eur. J. Immunol. 1987;17:375–383.

    Article  PubMed  CAS  Google Scholar 

  54. Ku CC, Kotzin B, Kappler J, Marrack P: CD8+ T cell clones in old mice. Immunol. Rev. 1997;160:139–144.

    Article  PubMed  CAS  Google Scholar 

  55. Mountz JD, Wu J, Zhou T, Hsu HC: Cell death and longevity: implications of Fas-mediated apoptosis in T cell senescence. Immunol. Rev. 1997;160:19–30,.

    Article  PubMed  CAS  Google Scholar 

  56. Wang E: Senescent human fibroblasts resist programmed cell death and failure to suppress Bcl2 is involved. Cancer Res. 1995;55:2284–2292.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine and Public Health, University of L’Aquila, Italy

    L. Ginaldi, M. De Martinis, A. D’Ostilio, L. Marini, M. F. Loreto, V. Martorelli & D. Quaglino

  2. Dipartimento di Medicina Interna e Sanità Pubblica, Univcrsità degli Studi dc L’Aquila, Via S.Sisto, 22/E, 67100, L’Aquila

    L. Ginaldi

Authors
  1. L. Ginaldi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. De Martinis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. D’Ostilio
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. Marini
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. F. Loreto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. V. Martorelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. D. Quaglino
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. Ginaldi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ginaldi, L., Martinis, M.D., D’Ostilio, A. et al. The immune S ystem in the elderly. Immunol Res 20, 109–115 (1999). https://doi.org/10.1007/BF02786467

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02786467

Key words

Search

Navigation