Skip to main content
SpringerLink
Log in

Immunophenotyping and T-cell proliferative capacity in a healthy aged population

  • Published:
Biogerontology Aims and scope Submit manuscript

Abstract

The age-related decline of immunological functions is well established but it remains largely unknown which specific changes are related to disease. We analyzed peripheral blood lymphocytes of 42 healthy elderly as well as 24 healthy young subjects from southern Brazil. No differences in phytohemagglutinin-induced proliferation and CD4:CD8 ratio were found between the subjects. However, CD4 expression (considering mean fluorescence intensity) was found up regulated in elderly subjects. No changes in activation molecules CD25, CD28, CD69 and CD95 were observed. A reduced proportion of naive (CD45RA+) T cells was found in the elderly compared to young subjects. No changes in adhesion molecule expression (CD11c and CD31) were observed. However, the frequencies of CD49d-positive cells, as well as expression of CD62L, were increased in the eldery subjects. We further described two subgroups of eldery subjects with an immunological risk profile defined by lower CD4:CD8 ratio and reduced proliferative response to mitogens. These data suggest that healthy aging is associated with intact T-cell proliferation and some compensatory immunophenotypical changes.

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

  • Alrayes H, Pachas W, Mirza N, Ahern DJ, Geha RS and Vercelli D (1992) IgE regulation and lymphokine patterns in aging humans. J Allerg Clin Immunol 90: 630-636

    Article  CAS  Google Scholar 

  • Aspinall R, Carroll J and Jiang S (1998) Age-related changes in the absolute number of CD95 positive cells in T-cell subsets in the blood. Exp Gerontol 33: 581-591

    Article  PubMed  CAS  Google Scholar 

  • Berthiaume F, Aparicio CL, Eungdamrong J and Yarmush ML (1999) Age-and disease - related decline in immune function: an opportunity for 'thyms-boosting' therapies. Tissue Eng 5: 499-514

    PubMed  CAS  Google Scholar 

  • Bodey B, Bodey B Jr, siegel SE and Kaiser HE (1997) Involution of the mammalian thymus one of the leading regulators of aging In Vivo 11: 421-440

    CAS  Google Scholar 

  • Boucher N, Dufeu-Duchesne T, Vicaut E, Farge D, Effros RB and Schächter F (1998) CD28 expression in T-cell aging and human longevity. Exp Gerontol 33: 267-282

    Article  PubMed  CAS  Google Scholar 

  • Cossarizza A, Ortolani C, Monti D and Franceschi C (1997) Cytometric analysis of immunosenescence. Cytometry 24: 297-313

    Article  Google Scholar 

  • De Martinis M, Modesti M, Loreto MF, Quaglino D and Ginaldi L (2000) Adhesion molecules on peripheral blood lymphocyte subpopulations in the elderly. Life Sci 68: 139-151

    Article  PubMed  CAS  Google Scholar 

  • Dennett NS, Barcia RN and McLeod JD (2002) Age associated decline in CD25 and CD28 expression correlate with an increased susceptibility to CD95 mediated apoptosis in T-cells. Exp Gerontol 37: 271-283

    Article  PubMed  CAS  Google Scholar 

  • Douziech N, Seres I, Larbi A, Szikszay E, Roy PM, Arcand M, Dupuis G and Fulop Jr T (2002) Modulation of human lymphocyte proliferative response with aging. Exp Gerontol 37: 369-387

    Article  PubMed  CAS  Google Scholar 

  • Dworsky R, Paganini-Hill A, Arthur Mand Parker J (1983) Immune responses of healthy humans 83-104 years of age. J Natl Cancer Inst 71: 265-268

    PubMed  CAS  Google Scholar 

  • Effros RB (1997) Loss of CD28 expression on T lymphocytes: a marker of replicative senescense. Develop Comp Immunol 21: 471-478

    Article  CAS  Google Scholar 

  • Fagiolo U, Amadori A, Biselli R, Paganelli R, Nisini E, Cozzi R, Zamarchi R and Damelio R (1993) Quantitative and qualitative analysis of anti-tetanus toxoid antibody response in the elderly-humoral immune response enhancement by thymostimulin. Vaccine 11: 1336-1340

    Article  PubMed  CAS  Google Scholar 

  • Fagnoni FF, Vescovini R, Passeri G, Bologna G, Pedrazzoni M, Lavagetto G, Casti A, Franceschi C, Passeri M and Sansoni P (2000) Shortage of circulating naive CD8(+) T cells provides new insights on immunodeficiency in aging. Blood 95: 2860-2868

    PubMed  CAS  Google Scholar 

  • Fahey JL, Schnelle JF, Boscardin J, Thomas JK, Gorre ME, Aziz N, Sadeghi H and Nishanian P (2000) Distinct categories of immunologic changes in frail elderly. Mech Ageing Dev 115: 1-20

    Article  PubMed  CAS  Google Scholar 

  • Ferguson FG, Wikby A, Maxson P, Olsson J and Jahansson B (1995) Immune parameters in a longitudinal study of a very old population of swedish people: a comparison between survivors and nonsurvivors. J Geront A Biol Sci Med Sci 50A: B378-B382

    Google Scholar 

  • Franceschi C, Monti D, Sansoni P and Cossarizza A (1995) The immunology of exceptional individuals: the lesson of centenarians. Immunol Today 16: 12-16

    Article  PubMed  CAS  Google Scholar 

  • French AL, McCullough ME, Rice KT, Schultz ME and Gordin FM (1998) The use of tetanus toxoid to elucidate the delayed-type hypersensitivity response in an older, immunized population. Gerontology 44: 56-60

    Article  PubMed  CAS  Google Scholar 

  • Fulop Jr T, Utsuyama M and Hirokawa, K (1991) Determination of interleukin 2 receptor number of Con A stimulated human lymphocytes with aging. Anonymous. Anonymous. J Clin Lab Immunol 34: 31-36

    PubMed  CAS  Google Scholar 

  • Ginaldi L, De Martinis M, Modesti M, Loreto F, Corsi MP and Quaglino D (2000) Immunophenotypical Changes of T Lymphocytes in the Elderly. Gerontology 46: 242-248

    Article  PubMed  CAS  Google Scholar 

  • Ginaldi L, Loreto MF, Corsi MP, Modesti M and De Martinis M (2001) Immunosenescence and infectious diseases. Microbes Infect 3: 851-857

    Article  PubMed  CAS  Google Scholar 

  • Hirokawa K, Utsuyama M, Kasai M, Kurashima C, Ishijima S and Zeng YX (1994) Understanding the mechanism of the agechange of thymic function to promote T cell differentiation. Immunol Lett 40: 269-277

    Article  PubMed  CAS  Google Scholar 

  • Huppert FA, Solomou W, O'Connor S, Morgan K, Sussams P and Brayne C (1998) Aging and lymphocyte subpopulations: wholeblood analysis of immune marker in a large population sample of healthy elderly individuals. Exp Gerontol 33: 593-600

    Article  PubMed  CAS  Google Scholar 

  • Kendall MD and Johson HRM (1980) The weight of the human thymus gland at necropsy. J Anat 313: 485-499

    Google Scholar 

  • Lehtonen J, Eskola J, Vainio O and Lehtonen A (1990) Changes in lymphocytes subsets and immune competence in very advanced age. J Gerontol 45: M108-M112

    PubMed  CAS  Google Scholar 

  • Ligthart GJ, Corberand JX, Fournier C, Galanaud P, Hijmans W, Kennes B, Müller-Hermelink HK and Steinmann GG (1984) Admission criteria for immunogerontological studies in man: the Senieur Protocol. Mech Ageing Dev 28: 47-55

    Article  PubMed  CAS  Google Scholar 

  • Mastroeni I, Vescia N, Pompa MG, Cattaruzza MS, Marini GP and Fara GM (1994) Immune response of the elderly to rabies vaccines. Vaccine 12: 518-520

    Article  PubMed  CAS  Google Scholar 

  • Mazari L and Lesourd BM (2002) Nutrional influences on immune response in healthy aged persons. Mech Ageing Dev 104: 25-40

    Article  Google Scholar 

  • Monti D, Troiano L, Grassilli E, Agnesini C, Tropea F, Barbieri D, Capri M, Cristofalo EA, Salvioli S, Ronchetti I, Bellomo G, Cossarizza A and Franceschi C (1992) Cell proliferation and cell death in immunosenescence. Ann N Y Acad Sci 663: 250-261

    PubMed  CAS  Google Scholar 

  • Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65: 55-63

    Article  PubMed  CAS  Google Scholar 

  • Nagel JE, Chrest FJ and Adler WH (1986) Enumeration of T lymphocytes subsets by monoclonal antibodies in young and aged humans. J Immunol 127: 2086-2088

    Google Scholar 

  • Negoro S, Hara H, Miyata S, Saiki O, Tanaka T, Yoshizaki K, Igarashi T and Kishimoto S (1986) 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. Mech Ageing Dev 36: 223-241

    Article  PubMed  CAS  Google Scholar 

  • O'Flynn K, Krensky AM, Beverley PC, Burakoff SJ and Linch DC (1985) Phytohemagglutinin activation of T cells through the sheep red blood cell receptor. Nature 313: 686-687

    Article  PubMed  Google Scholar 

  • Omenas E, Bakke P, Elsayed E, Hanoa R and Gulsvik A (1994) Total and specific serum IgE levels in adult: relationship to sex, age and environmental factors. Clin Exp Allergy 26: 530-539

    Article  Google Scholar 

  • Olsson J, Wikby A, Johansson B, Löfgren S, Nilsson B and Ferguson FG (2000) Age-related change in peripheral blood Tlymphocyte subpopulations and cytomegalovirus infection in the very old: the Swedish longitudinal OCTO immune study. Mech Ageing Dev 121: 187-201

    Article  PubMed  CAS  Google Scholar 

  • Pawelec G, Sansom D, Rehbein A, Adibzadeh M and Beckman I (1996) Decreased proliferative capacity and increased susceptibility to activation-induced cell death in late-passage human CD4+ TCR2+ cultured T-cell clones. Exp Gerontol 31: 655-668

    Article  PubMed  CAS  Google Scholar 

  • Pawelec G, Solana R, Remarque E and Mariani E (1998) Impact of aging on innate immunity. J Leuk Biol 64: 703-712

    CAS  Google Scholar 

  • Pawelec G, Wagner W, Adibzadeh M and Engel A (1999) T-cell immunosenescence in vitro and in vivo. Exp Gerontol 34: 419-429

    Article  PubMed  CAS  Google Scholar 

  • Pawelec G, Barnett Y, Forsey R, Frasca D, Globerson A, McLeod J, Caruso C, Franceschi C, Fülöp T, Gupta S, Mariani E, Mocchegiani E and Solana R (2002) T cells and aging. Front Biosci 7: d1056-d1018

    PubMed  CAS  Google Scholar 

  • Potestio M, Caruso C, Gervasi F, Scialabba G, D+Anna C, Di Lorenzo G, Balistreri CR, Candore C and Romano GC (1998) Apoptosis and ageing. Mech Ageing Dev 102: 221-237

    Article  PubMed  CAS  Google Scholar 

  • Rea IM, McNerlan SE and Alexander HD (1999) CD69, CD25, and HLA-DR activation antigen expression on CD3+ lymphocytes and relationship to serum TNF-, IFN-, and sIL-2R levels in aging. Exp Gerontol 34: 79-93

    Article  PubMed  CAS  Google Scholar 

  • Romano GC, Potestio M, Scialabba G, Mazzola A, Candore G, Lio D and Caruso C (2000) Early activation of? T lymphocytes in the elderly. Mech Ageing Dev 121: 231-238

    Article  PubMed  CAS  Google Scholar 

  • Sansoni P, Fagnoni F, Vescovini R, Mazzola M, Brianti V, Bologna G, Nigro E, Lavagetto G, Cossarizza A, Monti D, Franceschi C and Passeri M (1997) T lymphocyte proliferative capability to defined stimuli and costimulatory CD28 pathway is not impaired in healthy centenarians. Mech Ageing Dev 96: 127-136

    Article  PubMed  CAS  Google Scholar 

  • Saurwein-Teisl Mm, Lung TL, Marx F, Gschosser C, Asch E, Blasko I, Parson W, Bock Gg, Schonitzer D, Trannoy E and Grubeck-Loebenstein B (2002) Lack of antibody production following immunization in old age: association with CD8(+)CD28(-) T-cell clonal expansions and an imbalance in the production of TH1 and Th2 cytokines. J Immunol 168: 5893-5899

    Google Scholar 

  • Schatz 0D, Ellis T, Ottendorfer E, Jodoin E, Barrett D and Atkinson M (1998) Aging and the immune response to tetanus toxoid: diminished frequency and level of cellular immune reactivity to antigenic stimulation. Clin Diagn Lab Immunol 5: 894-896

    PubMed  CAS  Google Scholar 

  • Springer TA (1990) Adhesion receptors of the immune system. Nature 346: 425-434

    Article  PubMed  CAS  Google Scholar 

  • Tortorella C, Loria MP, Piazzolla G, Schulze-Koops H, Lipsky PE, Jirillo E and Antonaci S (1997) Age-related impairment of Tcell proliferative responses related to the decline of CD28+ T-cell subsets. Arch Gerontol Geriatr 26: 55-70

    Article  CAS  Google Scholar 

  • Valentine MA, Tsoukas CD, Rhodes G, Vaughan JH and Carson DA (1985) Phytohemagglutinin binds to the 20-kDa molecule of the T3 complex. Eur J Immunol 15: 851-854

    PubMed  CAS  Google Scholar 

  • Vie H and Miller RA (1986) Estimation by limiting dilution analysis of human IL-2-secreting T cells: detection of IL-2 produced by single lymphokyne-secreting T cells. J Immunol 136: 3292-3297

    PubMed  CAS  Google Scholar 

  • Yoshikawa TT (1997) Aging and infectious disease. Past, present and future. Infect Disease 176: 10553-1057

    Google Scholar 

  • Wada T, Seki H, Konno A, Ohta K, Nunogami K, Kaneda Y, Yachie A, Koizumi S, Taniguchi N and Miyawaki T (1998) Developmental changes and functional properties of human memory Tcell subpopulations defined by CD60 expression. Cell Immunol 187: 117-123

    Article  PubMed  CAS  Google Scholar 

  • Wikby A, Maxson P, Olsson J, Johansson B and Ferguson FG (1998) Changes in CD8 and CD4 lymphocyte subsets, T-cell proliferation responses and non-survival in the very old: the Swedish longitudinal OCTO-immune study. Mech Ageing Dev 102: 187-198

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departamento de Genética, Universidade Federal do Rio Grande do Sul, Brazil

    Alessandra Peres, Nance Beyer Nardi & José Artur Bogo Chies

  2. Pontifícia Universidade Católica do Rio Grande do Sul, Brazil

    Moisés Bauer

  3. Instituto de Geriatria e Gerontologia, Pontifícia Universidade Católica do Rio Grande do Sul, Brazil

    Ivana Beatrice da Cruz

Authors
  1. Alessandra Peres
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Moisés Bauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ivana Beatrice da Cruz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nance Beyer Nardi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. José Artur Bogo Chies
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to José Artur Bogo Chies.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Peres, A., Bauer, M., da Cruz, I.B. et al. Immunophenotyping and T-cell proliferative capacity in a healthy aged population. Biogerontology 4, 289–296 (2003). https://doi.org/10.1023/A:1026282917406

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1026282917406

Search

Navigation