Dysregulation of T-cell Function in the Elderly : Scientific Basis and Clinical Implications

Overview

Journal Drugs Aging

Specialties Geriatrics
Pharmacology

Date 2005 Jul 26

PMID 16038574

Citations 40

Authors

Tamas Fulop

Anis Larbi

Anders Wikby

Eugenio Mocchegiani

Katsuiku Hirokawa

Graham Pawelec

Affiliations

Soon will be listed here.

Abstract

The function of the immune system is to maintain body integrity by defending against infections, cancers, autoimmune diseases and inflammation-related chronic diseases. The immune response is known to become defective with aging, leading to decreased longevity and appearance of age-related disease. The most important changes occur in T-cell immunity, and are manifested particularly as altered clonal expansion of cells of limited antigen specificity. The causes of these alterations are multifactorial, and include thymic involution, T-cell subset changes and signal transduction alterations. The clinical consequences of these changes are not well defined, except for their extremely important negative impact on defence against infections, especially by new pathogens, and decreased responses to vaccination. Considering the public health consequences of decreased immune competence in old age, strategies for immune response modulation are desirable to decrease the health burden for the elderly and improve their quality of life.

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References

Zhang L, Conejo-Garcia J, Katsaros D, Gimotty P, Massobrio M, Regnani G . Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003; 348(3):203-13. DOI: 10.1056/NEJMoa020177. View

Nickoloff B, Nestle F . Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities. J Clin Invest. 2004; 113(12):1664-75. PMC: 420513. DOI: 10.1172/JCI22147. View

Wikby A, Johansson B, Ferguson F, Olsson J . Age-related changes in immune parameters in a very old population of Swedish people: a longitudinal study. Exp Gerontol. 1994; 29(5):531-41. DOI: 10.1016/0531-5565(94)90036-1. View

Lesourd B . Nutrition and immunity in the elderly: modification of immune responses with nutritional treatments. Am J Clin Nutr. 1997; 66(2):478S-484S. DOI: 10.1093/ajcn/66.2.478S. View

Castle S . Clinical relevance of age-related immune dysfunction. Clin Infect Dis. 2000; 31(2):578-85. DOI: 10.1086/313947. View

Pawelec G . Immunosenescence: impact in the young as well as the old?. Mech Ageing Dev. 1999; 108(1):1-7. DOI: 10.1016/s0047-6374(99)00010-x. View

Harman D . Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956; 11(3):298-300. DOI: 10.1093/geronj/11.3.298. View

Panossian L, Porter V, Valenzuela H, Zhu X, Reback E, Masterman D . Telomere shortening in T cells correlates with Alzheimer's disease status. Neurobiol Aging. 2002; 24(1):77-84. DOI: 10.1016/s0197-4580(02)00043-x. View

Langkamp-Henken B, Bender B, Gardner E, Herrlinger-Garcia K, Kelley M, Murasko D . Nutritional formula enhanced immune function and reduced days of symptoms of upper respiratory tract infection in seniors. J Am Geriatr Soc. 2003; 52(1):3-12. DOI: 10.1111/j.1532-5415.2004.52003.x. View

10.

Deveale B, Brummel T, Seroude L . Immunity and aging: the enemy within?. Aging Cell. 2004; 3(4):195-208. DOI: 10.1111/j.1474-9728.2004.00106.x. View

11.

Mocchegiani E, Muzzioli M, Giacconi R . Zinc, metallothioneins, immune responses, survival and ageing. Biogerontology. 2001; 1(2):133-43. DOI: 10.1023/a:1010095930854. View

12.

Hirokawa K, Utsuyama M, Kasai M, Kurashima C, Ishijima S, Zeng Y . Understanding the mechanism of the age-change of thymic function to promote T cell differentiation. Immunol Lett. 1994; 40(3):269-77. DOI: 10.1016/0165-2478(94)00065-4. View

13.

Franceschi C, Bonafe M, Valensin S . Human immunosenescence: the prevailing of innate immunity, the failing of clonotypic immunity, and the filling of immunological space. Vaccine. 2000; 18(16):1717-20. DOI: 10.1016/s0264-410x(99)00513-7. View

14.

Taner S, Onfelt B, Pirinen N, McCann F, Magee A, Davis D . Control of immune responses by trafficking cell surface proteins, vesicles and lipid rafts to and from the immunological synapse. Traffic. 2004; 5(9):651-61. DOI: 10.1111/j.1600-0854.2004.00214.x. View

15.

Effros R, Boucher N, Porter V, Zhu X, Spaulding C, WALFORD R . Decline in CD28+ T cells in centenarians and in long-term T cell cultures: a possible cause for both in vivo and in vitro immunosenescence. Exp Gerontol. 1994; 29(6):601-9. DOI: 10.1016/0531-5565(94)90073-6. View

16.

OMahony L, Holland J, Jackson J, Feighery C, Hennessy T, Mealy K . Quantitative intracellular cytokine measurement: age-related changes in proinflammatory cytokine production. Clin Exp Immunol. 1998; 113(2):213-9. PMC: 1905038. DOI: 10.1046/j.1365-2249.1998.00641.x. View

17.

Arlt W, Hewison M . Hormones and immune function: implications of aging. Aging Cell. 2004; 3(4):209-16. DOI: 10.1111/j.1474-9728.2004.00109.x. View

18.

Appay V, Dunbar P, Callan M, Klenerman P, Gillespie G, Papagno L . Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections. Nat Med. 2002; 8(4):379-85. DOI: 10.1038/nm0402-379. View

19.

Jonasson L, Tompa A, Wikby A . Expansion of peripheral CD8+ T cells in patients with coronary artery disease: relation to cytomegalovirus infection. J Intern Med. 2003; 254(5):472-8. DOI: 10.1046/j.1365-2796.2003.01217.x. View

20.

Pawelec G, Sansom D, Rehbein A, Adibzadeh M, Beckman I . Decreased proliferative capacity and increased susceptibility to activation-induced cell death in late-passage human CD4+ TCR2+ cultured T cell clones. Exp Gerontol. 1996; 31(6):655-68. DOI: 10.1016/s0531-5565(96)00097-6. View