Effect of aging on immunocompetent and inflammatory cells

Periodontology 2000

Volumn 16, Issue 1, 1998, Pages 53-79

  Mcarthur, William P ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

ANTIOXIDANT; CYTOKINE; OXIDIZING AGENT;

AGED; AGING; DENTAL CARE; HUMAN; IMMUNITY; IMMUNOLOGY; LEUKOCYTE; METABOLISM; MUCOSAL IMMUNITY; PHYSIOLOGY; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE; VACCINATION;

AGED; AGED, 80 AND OVER; AGING; ANTIOXIDANTS; CYTOKINES; DENTAL CARE FOR AGED; HUMANS; IMMUNITY; IMMUNITY, MUCOSAL; LEUKOCYTES; OXIDANTS; SIGNAL TRANSDUCTION; T-LYMPHOCYTES; VACCINATION;

EID: 0031987873     PISSN: 09066713     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1600-0757.1998.tb00116.x     Document Type: Article

References (214)

1. Adihzadeh M, Mariani E, Bartoloni C, Beckman I, Lighthart G, Remarque E, Shall S, Solana R, Taylor GM, Barnell Y, Pawelec G. Lifespans of T lymphocytes. Mech Ageing Dev 1996: 91: 145-154.
2. Albright JW, Albright JF. Age-associated impairment of murine natural killer activity. Proc Natl Acad Sci U S A 1983: 80: 6371-6375.
3. Ames BN, Shigenaga NK. Oxidants are a major contributor to aging. Ann N Y Acad Sci 1992: 663: 85-95.
4. Ames BN, Shigenaga MK, Hagen TM, Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci U S A 1993: 90: 7915-7922.
5. Andrew ME, Coupar BEA, Boyle DB, Ada GL. The roles of influenza virus hemagglutinin and nuclear protein: analysis using vaccinia virus recombinants. Scand J Immunol 1987: 25: 21-28.
6. Araneo B, Dowell T, Woods ML, Daynes R, Judd M, Evans T. DHEAS as an effective vaccine adjuvant in elderly humans. Ann N Y Acad Sci 1995: 774: 232-248.
7. Arnon A, Levi R. Synthetic recombinant vaccines against viral agents. Int Arch Allergy Immunol 1995: 108: 321-326.
8. Arranz FE, O'Mahony S, Barton JR, Ferguson A. Immunosenescence and mucosal immunity: significant effect of old age on secretory IgA concentrations and intraepithelial lymphocyte counts. Gut 1992: 33: 882-886.
9. Artur K, Herbeth B, Guémouri L, Lecomte E, Jeandel C. Siest G. Age-related variations of enzymatic defenses against free radicals and peroxides. In: Emerit I, Chance B, ed. Free radicals and aging. Basel: Birkhäuser, 1992: 359-367.
10. Beckman I, Shepard K, Firgaira F, Ahern M. Age-related defects in CD2 receptor-induced activation in human T-cell subsets. Immunology 1995: 86: 533-536.
11. Beiqing L, Chen M, Whisler RL. Sublethal levels of oxidative stress stimulates transcriptional activation of c-jun and suppress IL-2 promoter activation in Jurkat T cells. J Immunol 1996: 157: 160-169.
12. Beiqing L, Cornwell DG, Whisler RL. Age-related changes in DNA of human T cells: accelerated unwinding of double-strand DNA after oxidant stress and identification of DNA fragmentation resembling apoptosis. Aging Immunol Infect Dis 1992: 3: 101-116.
13. Bendich A. Physiological role of antioxidants in the immune system. J Dairy Sci 1993: 76: 2789-2794.
14. Bhooma T, Krishnaraj R, Svanborg A. Cytokine sensitivity of human NK cells during immunosenescence. I. IL-2 induced anti-tumor cytotoxicity. Aging Immunol Infect Dis 1994: 5: 83-97.
15. Biselli R, Fagiolo U, Nisini R, Paganelli R, D'Offizi G, Ferrara R, Bertollo L, D'Amello R. Humoral response to influenza hemagglutinin: oligoclonal spectrotype and failure of thymopentin as immunoadjuvant. Gerontol 1995: 41: 3-10.
16. Bloom ET. Natural killer cells, lymphokine-associated killer cells, and cytolytic T lymphocytes: compartmentalization of age-related changes in cytolytic lymphocytes? J Gerontol 1994: 49: 1385-1392.
17. Blumberg JB. Interactions between vitamin E, free radicals, and immunity during the aging process. Adv Exp Med Biol 1994: 366: 325-333.
18. Borrego F, Pena J, Solana R. Regulation of CD69 expression on human natural killer cells: differential involvement of protein kinase C and protein tyrosine kinases. Eur J Immunol 1993: 23: 1039-1043.
19. Brady LJ, Walker C, Oxford GE, Stewart C, Magnusson I, McArthur W. Oral diseases, mycology, and periodontal microbiology of HIV-1 infected women. Oral Microbiol Immunol 1996: 11: 371-380.
20. Broome CV, Breiman RF. Pneumococcal vaccine-past, present, and future. N Engl J Med 1991: 325: 1506-1508.
21. Brouwer A, Knook DL. The reticuloendothelial system and aging: a review. Mech Ageing Dev 1983: 21: 205-228.
22. Brunk UT, Jones CB, Sohal RS. Fluorescent pigments, thought to be due to crosslinks between protein and lipid peroxidation products, are increased in aging. Mutat Res 1992: 275: 395-403.
23. Burt BA. Periodontitis and aging: Reviewing recent evidence. J Am Dent Assoc 1994: 125: 273-279.
24. Burt D. Engineered vaccines for immunization of the elderly. Aging Immunol Infect Dis 1994: 5: 61-67.
25. Burton GF, Kosco MH, Szakal AK, Tew JG. Iccosomes and the secondary antibody response. Immunology 1991: 73: 271-276.
26. Cakman I, Rohwer J, Schutz RM, Kirschner H, Rinnk L. Dysregulation between Th1 and Th2 cell populations in the elderly. Mech Ageing Dev 1996: 87: 197-210.
27. Canfield LM, Forage JW, Valenzuela JG. Carotenoids as cellular antioxidants. Proc Soc Exp Biol Med 1992: 200: 260-265.
28. Challacombe SJ, Percival RS, Marsh PD. Age-related changes in immunoglobulin isotypes in whole and parotid saliva and serum in healthy individuals. Oral Microbiol Immunol 1993: 10: 202-207.
29. Chen Y, Ramsey MA, Bradley SE Differential monokine production by macrophages from aged mice stimulated with various microorganisms. Aging Immunol Infect Dis 1993: 4: 155-167.
30. Chopra RK, Holbrook NJ, Powers DC, McCoy MT, Alder WH, Nagel JE. Interleukin 2, interleukin 2 receptor and interferon-γ synthesis and mRNA expression in phorbol myristate acetate and calcium ionophore A23187-stimulated T-cell from elderly humans. Clin Immunol Immunopathol 1989: 53: 297-308.
31. Ciccone E, Pende D, Viale O, DiDonato C, Tripodi G, Orengo AM, Guardiola J, Moretta A, Moretta L. Evidence of a natural killer (NK) cell repertoire for (allo) antigen recognition: definition of five distinct NK-determined allo-specificities in humans. J Exp Med 1992: 175: 709-718.
32. Clark JA, Peterson TC. Cytokine production and aging: overproduction of IL-8 in elderly males in response to lipopolysaccharide. Mech Ageing Dev 1994: 77: 127-139.
33. Clerici M, Shearer GM. A Th1 to Th2 switch is a critical step in the etiology of HIV infection. Immunol Today 1993: 14: 107-110.
34. Cohen HJ, Boland KM, Rao KM. Age-related studies of SIg, Leu-4, and concanavalin A receptor densities and capping in human lymphocytes. Mech Ageing Dev 1991: 59: 253-262.
35. Connault L, Preudhomme J-L, Gombert J, Aperce J-M, Aucouturier P. Serum monoclonal immunoglobulins in healthy aged people: a study of incidence and isotyping using a sensitive immunoblotting method. Aging Immunol Infect Dis 1991: 3: 37-42.
36. Corberand JX, Laharrague PR Fillola G. Neutrophils of healthy aged humans are normal. Mech Ageing Dev 1986: 36: 57-63.
37. Cossarizza A, Barbieri D, Londei M. T cell repertoire usage in humans, from newborns to centenarians. Int Rev Immunol 1995: 12: 41-55.
38. + T cells throughout life, from newborns to centenarians: implications for T cell memory. Mech Ageing Dev 1996: 86: 173-195.
39. Dalemans W, Delers A Delmelle C, Denamur F, Meykens R, Thiriart C, Veenstra S, Francotte M, Bruck C, Cohen J. Protection against homologous influenza challenge by genetic immunization with SFV-RNA encoding Flu-HA. Ann N Y Acad Sci 1995: 772: 255-256.
40. Daynes RA, Araneo BA. Prevention and reversal of some age associated changes in immunologic responses by supplemental dehydroepiandrosterone sulfate therapy. Aging Immunol Infect Dis 1992: 3: 135-153.
41. Daynes RA, Arameo BA, Ershler WB, Maloney C, Li GZ, Ryn SY. Altered regulation of IL-6 production with normal aging. Possible linkage to the age-associated decline in dehydroepiandrosterone and its sulfated derivative. J Immunol 1993: 150: 5219-5230.
42. Dobber R, Tielemans M, Nagelkerken L. The in vivo effects of neutralizing antibodies against IFN-gamma, IL-4, or IL-10 on the humoral immune response in young and aged mice. Cell Immunol 1995: 160: 185-192.
43. Enwonwu CO, Meeks VI. Bionutrition and oral cancer in humans. Crit Rev Oral Biol Med 1995: 6: 5-17.
44. Ershler WB. Influenza vaccination in the elderly: can efficacy be enhanced? Geriatrics 1988: 43: 79-83.
45. Ershler WB. Interleukin-6: a cytokine for gerontologists. J Am Geriatr Soc 1993: 41: 176-181.
46. Ershler WB, Sun WH, Binkley N. The role of interleukin-6 in certain age-related diseases. Drugs Aging 1994: 5: 358-365.
47. Ertl HC, Xiang ZQ. Genetic immunization. Viral Immunol 1996: 9: 1-9.
48. Fabris N, Mocchegiani E. Zinc, human diseases and aging. Aging 1995: 7: 77-93.
49. Fabris N. Biomarkers of aging in the neuroendocrine-immune domain. Time for a new theory of aging? Ann N Y Acad Sci 1992: 663: 335-348.
50. + (CD16) large granular lymphocytes and decreased NK activity during human aging. Clin Exp Immunol 1987: 68: 340-347.
51. Fagliolo U, Amadori A Biselli R, Paganelli R, Nisini R, Cozzi E, Zamarchi R, D'Amelio R. Quantitative and qualitative analysis of anti-tetanus toxoid antibody response in the elderly. Humoral immune response enhancement by thymostimulin. Vaccine 1993: 11: 1336-1340.
52. Fagiolo U, Amadori A, Cozzi E, Bendo R, Lama M, Douglas A, Palu G. Humoral and cellular immune response to influenza virus vaccination in aged humans. Aging Milano 1993: 5: 451-458.
53. Fagiolo U, Cossarizza C, Scala E, Fanales-Belasio E, Ortolani C, Cozzi E, Monti D Franceschi C, Paganelli R. Increased cytokine production in mononuclear cells of healthy elderly people. Eur J Immunol 1993: 23: 2375-2378.
54. Ferguson FG, Wikby A, Maxson P, Olsson J, Johansson B. Immune parameters in a longitudinal study of a very old population of Swedish peoples: a comparison between survivors and nonsurvivors. J Gerontol A Biol Sci Med Sci 1995: 50A: B378-B382.
55. Franceschi C, Cossarizza A. Introduction: the reshaping of the immune system with age. Int Rev Immunol 1995: 12: 1-4.
56. Franceshi C, Monti D, Barbieri D, Negro SSP, Capri M, Guido M, Azzi R, Paganelli SPR, Fagiolo U, Baggio G, Donazzan S, Mariotti S, D'Addato S Gaddi A, Ortolani C, Cossarizza A. Immunosenescence in humans: deterioration or remodeling? Int Rev Immunol 1995: 12: 57-74.
57. Franceschi C, Monti D, Cossarizza A, Fagnoni F, Passeri G, Sansoni P. Aging, longevity, and cancer: studies in Down's syndrome and centenarians. Ann N Y Acad Sci 1991: 621: 428-440.
58. Franceschi C, Monti D, Sansoni P, Cossarizza A. The immunology of exceptional individuals: the lesson of centenarians. Immunol Today 1995: 16: 12-16.
59. Franceschi C, Monti D, Scarfi MR, Zeni O, Temperani P, Emilia G, Sansoni P, Lioi MB, Troiano L, Agnesini C, Salvioli S, Cossarizza A. Genomic instability and aging. Studies in centenarians (successful aging) and in Down's syndrome patients (accelerated aging). Ann N Y Acad Sci 1992: 663: 4-16.
60. Frasca D, Guidi L, Bartoloni C, Triceri A, Vangeli M, Antico L, Carbonin PU, Errani A, Doria G. Age-related modulation of cytokine production, IL-2R expression and function in a population of healthy subjects (22 to 97 years). Aging Immunol Infect Dis 1994: 5: 3-12.
61. Friedman EM, Invin MR. A role for CRH and the sympathetic nervous system in stress-induced immunosuppression. Ann N Y Acad Sci 1995: 771: 396-418.
62. Fulop T. Signal transduction changes in granulocytes and lymphocytes with ageing. Immunol Lett 1994: 40: 259-268.
63. Fulop T, Barabas G, Varga Z, Jozsef C, Csabina S, Szues S, Seres I, Szikszay E, Jeney Z, Penyige A. Age-dependent changes in transmembrane signalling: identification of G proteins in human lymphocytes and polymorphonuclear leukocytes. Cell Signal 1993: 5: 593-603.
64. Fulop T, Leblanc C, Lacombe G, Dupruis G. Cellular distribution of protein kinase C isozymes in CD3-mediated stimulation of human T-lymphocytes with aging. FEBS Lett 1995: 375: 69-74.
65. Fulop T, Utsuyma M, Hirokawa K. Determination of interleukin 2 receptor number on Con A stimulated human lymphocytes with aging. J Clin Lab Immunol 1991: 34: 31-36.
66. Gamble DA, Schwab R, Weksler ME, Szabo P. Decreased steady state c-myc mRNA in activated T cell cultures from old humans is caused by a smaller proportion of T cells that transcribe the c-myc gene. J Immunol 1990: 144: 3569-3573.
67. Garg M, Bondada S. Reversal of age-associated decline in immune response to Pnu-Imune vaccine by supplementation with the steroid hormone dehydroepiandrosterone. Infect Immun 1993: 61: 2238-2241.
68. Garg M, Kaplan AM, Bondada S. Cellular basis of differential responsiveness of lymph nodes and spleen to 23-valent Pnu-Imune vaccine. J Immunol 1994: 152: 1589-1596.
69. Garg M, Luo W, Kaplan AM, Bondada S. Cellular basis of decreased immune responses to pneumococcal vaccines in aged mice. Infect Immun 1996: 64: 4456-4462.
70. Gillespie SH. Aspects of pneumococcal infection including bacterial virulence, host response, and vaccination. J Med Microbiol 1989: 28: 237-248.
71. Glathe H, Bigl S, Grosche A. Comparison of humoral immune responses to trivalent influenza split vaccine in young, middle-aged and elderly people. Vaccine 1993: 11: 702-705.
72. Globerson A. Thymocyte progenitors in ageing. Immunol Lett 1994: 40: 219-224.
73. Globerson A. T lymphocytes and aging. Int Arch Allergy Immunol 1995: 107: 491-497.
74. Goldberg TH, Baker DG, Schumacher HR. Interleukin 1 and the immunology of aging. Aging Immunol Infect Dis 1991: 3: 81-89.
75. Grigolo B, Borzi RM, Mariani E, Monaco MC, Cattini L, Porstmann T, Facchini A. Intracellular Cu/Zn superoxide dismutase levels in T and non-T cells from normal aged subjects. Mech Ageing Dev 1994: 73: 27-37.
76. Grist SA, McCarron M, Kutlaca A, Turner DR, Morley AA. In vivo human somatic mutation: frequency and spectrum with age. Mutat Res 1992: 266: 189-196.
77. Grossman A, Rabinovitch PS, Kavanagh TJ, Jinneman JC, Gilliland LK, Ledbetter JA, Kanner SB. Activation of murine T-cells via phospholipase-c gamma 1-associated protein tyrosine phosphorylation is reduced in aging. J Gerontol A Biol Sci Med Sci 1995: 50: 205-212.
78. + memory and naive T lymphocyte proliferative responses to both mitogen and recall antigens in healthy humans. Aging Immunol Infect Dis 1994: 5: 109-119.
79. Hallgren HM, Bergh N, Rodysill KJ, O'Leary JJ. Lymphocyte proliferative response to PHA and anti-CD3/Ti monoclonal antibodies, T cell surface marker expression, and serum IL-2 receptor levels as biomarkers of age and health. Mech Ageing Dev 1988: 43: 175-185.
80. Hartwig M, Steinmann G. On a casual mechanism of chronic thymic involution in man. Mech Ageing Dev 1994: 75: 151-156.
81. Hennebold JD, Daynes RA. Regulation of macrophage dehydroepiandrosterone sulfate metabolism by inflammatory cytokines. Endocrinol 1994: 135: 67-75.
82. Hijmans W, Radl J, Bottazzo GF, Doniach D. Autoantibodies in highly aged humans. Mech Ageing Dev 1984: 26: 83-89.
83. Holmes KL, Schnizlein CT, Perkins EH, Tew JG. The effect of age on antigen retention in lymphoid follicles and in collagenous tissues of mice. Mech Ageing Dev 1984: 25: 243-255.
84. Huang YP, Gauthey L, Michel M, Loreto M, Paccaud M, Pechere JC, Michel JP. The relationship between influenza vaccine-induced specific antibody responses and vaccine-induced nonspecific autoantibody responses in healthy older women. J Gerontol 1992: 47: 50-55.
85. Huang YP, Pechere JC, Michel M, Gauthey L, Loreto M, Curran JA, Michel JP. In vivo T cell activation, in vitro defective IL-2 secretion, and response to influenza vaccination in elderly women. J Immunol 1992: 148: 715-722.
86. Huber LA, Yu QB, Jurgen G, Bock G, Buhler E, Gey KF, Schonitzer D, Traill KN, Wick G. Correlation of lymphocyte lipid composition membrane microviscosity and mitogen response in the aged. Eur J Immunol 1991: 21: 2761-2765.
87. Kawanishi H. Recent progress in senescence-associated gut mucosal immunity. Dig Dis Sci 1993: 11: 157-172.
88. Kiecolt-Glaser JK, Glaser R, Gravenstein S, Malarkey WB, Sheridan J. Chronic stress alters the immune response to influenza virus vaccine in older adults. Proc Natl Acad Sci USA 1996: 93: 3043-3047.
89. cdc2 in T lymphocytes. J Immunol 1992: 149: 17-23.
90. Kishimoto S, Tomino S, Mitsuya H, Fujiwara H, Tsuda H. Age-related decline in the in vitro and in vivo synthesis of anti-tetanus toxoid antibody in humans. J Immunol 1980: 125: 2347-2352.
91. Kishimoto S, Tomino S, Mitsuya H, Nishimura H. Age-related decrease in frequencies of B-cell precursors and specific helper T-cells involved in the IgG anti-tetanus toxoid antibody production in humans. Clin Immunol Immunopathol 1982: 25: 1-10.
92. Klinman NR. The basis for decreased B cell responsiveness with aging: the legacy and the challenge. Aging Immunol Infect Dis 1994: 5: 203-210.
93. Konradsen HB. Quantity and avidity of pneumococcal antibodies before and up to five years after pneumococcal vaccination of elderly persons. Clin Infect Dis 1995: 21: 616-620.
94. Krishnaraj R, Blandford G. Age-associated alterations in human natural killer cells. 1. Increased activity as per conventional and kinetic analysis. Clin Immunol Immunopathol 1987: 45: 268-285.
95. Kurashima C, Utsuyama M, Kasai M, Ishijima SA, Konno A, Hirokawa K. The role of thymus in the aging of Th cell subpopulations and age-associated alteration of cytokine production by these cells. Int Immunol 1995: 7: 97-104.
96. Kutza J, Murasko DM. Age-associated decline in IL-2 and IL-12 induction of LAK cell activity of human PBMC samples. Mech Ageing Dev 1996: 90: 209-222.
97. Lander ES. The new genomics: global views of biology. Science 1996: 274: 536-539.
98. Levy SM, Herberman RB, Lee J, Whiteside T, Beadle M, Heiden L, Simons A. Persistently low natural killer cell activity, age, and environmental stress as predictors of infectious morbidity. Nature Immun Cell Growth Regul 1991: 10: 289-307.
99. Ligthart GJ. The immune system in aging: the need to consider health status in gerontologic studies: the SENIEUR protocol. Aging Immunol Infect Dis 1994: 5: 161-171.
100. Ligthart GJ, Corberand JX, Founier C, Garanaud P, Hijmans W, Kennes B, Muller-Hermelink HK, Steinmann GG. Admission criteria for immunogerontological studies in man: the SENIEUR protocol. Mech Ageing Dev 1984: 28: 47-55.
101. Ligthart GJ, Corberand JX, Geertzen HG, Meinders AE, Knook DL, Hijmans W. Necessity of the assessment of health status in human immunogerontological studies: evaluation of the SENIEUR protocol. Mech Ageing Dev 1990; 55: 89-97.
102. Ligthart GJ, Radl J, Corberand TX, Van Nieuwkoop JA, Van Staalduinen GJ, Wesselman vanHelmand DJ, Hijmans W. Monoclonal gammopathies in human aging: increased occurrence with age and correlation with health status. Mech Ageing Dev 1990: 52: 235-243.
103. Ligthart GJ, Schuit HRE, Hijmans W. Subpopulations of mononuclear cells in ageing: expansion of the null cell compartment and decrease in the number of T and B cells in human blood. Immunol 1985: 55: 15-21.
104. Ligthart GJ, Schuit HRE, Hijmans W. Natural killer cell function is not diminished in the healthy aged and is proportional to the number of NK cells in the peripheral blood. Immunology 1989: 68: 396-402.
105. Ligthart GJ, VanVlokoven PC, Schuit HRE, Hijmans W. The expanded null cell compartment in ageing: increases in the number of killer cells and changes in T-cell and NK-cell subsets in human blood. Immunol 1986: 59: 353-357.
106. Lio D, Candore G, Cigna D, D'Anna C, DiLorenzo G, Giordano C, Lucania G, Mansueto P, Melluso M, Assunta Modica M, Caruso C. In vitro T-cell activation in elderly individuals: failure in CD69 and CD71 expression. Mech Ageing Dev 1996: 89: 51-58.
107. Liyama M, Shimada Y, Kita T, Ito H. Effect of aging on macrophage adherence to extracellular matrix proteins. Mech Ageing Dev 1992: 66: 149-158.
108. Lustyik G, O'Leary JJ. Aging and the immobilization of intracellular calcium by phytohemagglutinin in human T cells. J Gerontol 1989: 44: B30-B36.
109. Lyngbye J, Kroll J. Quantitative immunoelectrophoresis of proteins in serum from a normal population: season-, age- and sex-related variations. Clin Chem 1971: 17: 495-500.
110. Mariani E, Monaco MC, Cattini L, Sinoppi M, Facchini A. Distribution and lytic activity of NK cell subsets in the elderly. Mech Ageing Dev 1994: 76: 177-187.
111. Mariotti S, Barbesino G, Caturegli P, Bartalena L, Sansoni P, Faynoni F, Monti D, Fagiolo U, Franceschi C, Pinchera A. Complex alteration of thyroid function in healthy centenarians. J Clin Endocrinol Metab 1993: 77: 1130-1134.
112. Mariotti S, Sansoni P, Barbesino G, Caturegli P, Monti D, Cossarizza A, Giacomelli T, Passeri P, Fagiolo U, Pinchera A, Franceschi C. Thyroid and other organ-specific auto-antibodies in healthy centenarians. Lancet 1992: 339: 1506-1508.
113. McArthur WP, Bloom C, Taylor M, Smith J, Wheeler T, Magnusson NI. Antibody responses to suspected periodontal pathogens in elderly subjects with periodontal disease. J Clin Periodontol 1995: 22: 842-849.
114. McArthur WP, Bloom K. Taylor M, Wheeler T, Smith J, Magnusson NI. Peripheral blood leukocyte populations in the elderly with and without periodontal disease. J Clin Periodontol 1996: 23: 846-852.
115. McClure JE, Lameris N, Wara DW, Goldstein AL. Immunochemical studies on thymosin: radioimmunoassay of thymosin alpha-1. J Immunol 1982: 128: 368-375.
116. McElhaney JE, Meneilly GS, Lechelt KE, Bleackly RC. Split virus influenza vaccines: do they provide adequate immunity in the elderly? J Gerontol 1994: 49: 37-43.
117. McElhaney JE, Meneilly GS, Pinkoski MJ, Lechelt KE, Bleackley RC. Vaccine related determinants of the interleukin-2 response to influenza vaccination in healthy young and elderly adults. Vaccine 1995: 13: 6-10.
118. Meydani SM. Micronutrients and immune function in the elderly. Ann N Y Acad Sci 1990: 587: 196-206.
119. Meydani SN, Barkland MP, Liu S. Vitamin E supplementation enhances cell-mediated immunity in healthy elderly subjects. Ann J Clin Nutr 1990: 52: 557-563.
120. Meydani SN, Wu D, Santos MS, Hayek MG. Antioxidants and immune response in aged persons: overview of present evidence. Am J Clin Nutr 1995: 62: 1462S-1476S.
121. Miller RA. Aging and immune function: cellular and biochemical analyses. Exp Gerontol 1994: 29: 21-35.
122. Miller RA. Physiology of aging. In Masoro E, ed. Handbook of physiology. Section II. New York: Oxford University Press, 1995: 555-570.
123. Miller RA. The aging immune system: primer and prospectus. Science 1996: 273: 70-74.
124. Miller RA. Accumulation of hyporesponsive, calcium extruding memory T cells as a key feature of age-dependent immune dysfunction. Clin Immunol Immunopathol 1991: 58: 305-317.
125. Miyasaki KT. The neutrophil: mechanisms of controlling periodontal bacteria. J Periodontol 1991: 62: 761-774.
126. Mocchegiani E, Fabris N. Age-related thymus involution: zinc reverses in vitro the thymulin secretion defect. Int J Immunopharmacol 1995: 17: 745-749.
127. Mocchegiani E, Santarelli L, Muzzioli M, Fabris N. Reversibility of the thymic involution and of age-related peripheral immune dysfunctions by zinc supplementation of old mice. Int J Immunopharmacol 1995: 17: 703-718.
128. Mohasci A, Fulop T, Kozlovszky B, Sere I, Leovey A. Superoxide anion production and intracellular free calcium levels in resting and stimulated polymorphonuclear leukocytes obtained from healthy and arteriosclerotic subjects of various ages. Clin Biochem 1992: 25: 285-288.
129. Monti D, Troiano L, Grassilli E, Agnesini C, Tropea F, Barbieri D, Capri M, Salvioli S, Ronchetti I, Bellomo G, Cossarizza A, Franceschi C. Cell proliferation and cell death in immunosenescence. Ann N YAcad Sci 1992: 663: 250-261.
130. Moretta L, Ciccone E, Moretta A, Hoglund P, Ohlen C, Karre K. Allorecognition by NK cells: nonself or no self? Immunol Today 1992: 13: 300-306.
131. Morley JE, Powers DC. Psychoneuroimmunology and aging. J Am Geriatr Soc 1993: 41: 572-573.
132. Murasko DM, Goonewardene IM. T-cell function in aging: mechanisms of decline. Annu Rev Gerontol Geriatr 1990: 10: 71-96.
133. Nafziger J, Bessege JP, Guillosson JJ, Damais C, Lesourd B. Decreased capacity of IL-1 production by monocytes of infected elderly patients. Aging Immunol Infect Dis 1993: 4: 25-34.
134. Nagel JE, Chopra RK, Chrest FJ, McCoy MT, Schneider EL, Kolbrook NJ, Adler WK. Decreased proliferation, interleukin-2 synthesis and interleukin-2 receptor expression are accompanied by decreased mRNA expression in phytohemagglutinin-stimulated cells from elderly donors. J Clin Invest 1988: 81: 1096-1102.
135. Nagel JE, Chopra RK, Powers DC, Adler W. Effect of age on the human high affinity interleukin 2 receptor of phytohemagglutinin stimulated peripheral blood lymphocytes. Clin Exp Immunol 1989: 75: 286-291.
136. Nakahama M, Mohri N, Mori S, Shindo G, Yokoi Y, Machinami R. Immunohistochemical and histometrical studies of the human thymus with special emphasis on age-related changes in medullary epithelial and dendritic cells. Virchows Arch B Cell Pathol 1990: 58: 245-251.
137. Nielsen H, Blom J, Larsen SO. Human blood monocytes function in relation to age. APMIS 1984: 92: 5-10.
138. high T cell population. Eur J Immunol 1993: 23: 1057-1063.
139. O'Leary JJ, Fox R, Bergh N, Rodysill KJ, Hallgren HM. Expression of human T cell antigen receptor complex in advanced age. Mech Ageing Dev 1988: 45: 239-252.
140. Olshansky SJ, Carnes BA, Cassel C. In search of Methuselah: estimating the upper limits to human longevity. Science 1990: 250: 634-640.
141. Orentriech N, Brind JL, Rizer RL, Vogelman JH. Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. J Clin Endrocrinol Metab 1984: 59: 551-555.
142. Pagnelli R, Quinti I, Fagiolo U, Cossarizza A, Ortolani C, Guerra E, Sansoni P, Pucillo LP, Scalla E, Cozzi E, Bertoli L, Monti D, Franceschi C. Changes in circulating B cells and immunoglobulin classes and subclasses in a healthy aged population. Clin Exp Immunol 1992: 90: 351-354.
143. Paganelli R, Scala E, Quinti I, Ansotegui IJ. Humoral immunity in aging. Aging Milano 1994: 6: 143-150.
144. + T cells in human longevity: studies on two healthy centenarians. Eur J Immunol 1996: 26: 2030-2034.
145. Pahlavani MA, Richardson A. The effect of age on the expression of interleukin-2. Mech Ageing Dev 1996: 89: 125-154.
146. + channel activity in aged humans. Biochem Biophys Res Commun 1994: 199: 519-524.
147. Pawelec G, Adibzadeh M, Pohla H, Schaudt K. Immunosenescence: ageing of the immune system. Immunol Today 16: 420-422.
148. Penn ND, Purkins L, Kelleher J, Heatley RV, Mascie-Taylor BH, Belfield PW. Ageing and duodenal mucosal immunity. Age Ageing 1991: 20: 33-36.
149. Pinchera A, Mariotti S, Barbesino G, Bechi R, Sansoni P,. Fagiolo U, Cossarizza A, Franceschi C. Thyroid autoimmunity and ageing. Horm Res 1995: 43: 64-68.
150. Posnett DN, Sinha R, Kabak S, Russo C. Clonal population of T cells in normal elderly humans: the T cell equivalent to "benign monoclonal gammopathy". J Exp Med 1994: 179: 609-618.
151. Post DJ, Carter KC, Papaconstantinou J. The effect of aging on constitutive mRNA levels and lipopolysaccharide inducibility of acute phase genes. Ann N Y Acad Sci 1991: 621: 66-77.
152. Powers DC. Immunologic principles and emerging strategies of vaccination for the elderly. J Am Geriatr Soc 1992: 40: 81-94.
153. Powers DC. Influenza A virus-specific cytotoxic T lymphocyte activity declines with advancing age. J Am Geriatr Soc 1993: 41: 1-5.
154. Powers DC. Effect of age on serum immunoglobulin G subclass antibody responses to inactivated influenza virus vaccine. J Med Virol 1994: 43: 57-61.
155. Powers DC, Belshe RB. Effect of age on cytotoxic T-lymphocyte memory as well as serum and local antibody responses elicited by inactivated influenza virus vaccine. J Infect Dis 1993: 167: 584-592.
156. Powers DC, Morley JE, Flood JF. Age-related changes in LFA-1 expression, cell adhesion, and PHA-induced proliferation by lymphocytes from senescence-accelerated mouse (SAM)-P/8 and SAM-R/1 substrains. Cell Immunol 1992: 141: 444-456.
157. Provinciali M, Di-Stefano G, Colombo M, Della-Croce F, Gandolfi MC, Daghetta L, Anichini M, Della-Bitta R, Fabris N. Adjuvant effect of low-dose interleukin 2 on antibody response to influenza virus vaccination in healthy elderly subjects. Mech Ageing Dev 1994: 77: 75-82.
158. Provinciali M, Muzzioli M, Di-Stefano G, Fabris N. Recovery of spleen cell natural killer activity by thyroid hormone treatment in old mice. Nature Immun Cell Growth Regul 1991: 10: 226-236.
159. Quadri RA, Piastre O, Phelouzal MA, Arbogast A, Proust JJ. Age-related tyrosine-specific protein phosphorylation defect in human T-lymphocytes activated through CD3, CD4, CD8, or the IL-2 receptor. Mech Ageing Dev 1996: 88: 125-138.
160. Rabinowich H, Goses Y, Reshef T, Klajman A. Interleukin 2 production and activity in aged humans. Mech Ageing Dev 1985: 32: 213-226.
161. Radl J, Sepers JK, Skvaril F, Morrell A, Hijmans W. Immunoglobulin patterns in humans over 94 years of age. Clin Exp Immunol 1975: 22: 84-90.
162. Rea IM. Age and sex changes in neutrophil function. Aging Immunol Infect Dis 1988: 1: 121-130.
163. Richter M, Jodouin C-A. The delay in the synthesis and secretion of immunoglobulins by the B cells of healthy ambulatory elderly is due to subtle defects in the null cells and the B cells. Aging Immunol Infect Dis 1993: 4: 1-16.
164. Roberts-Thomson IC, Whittingham S, Youngchaiyud U, MacKay IR. Aging, immune response, and mortality. Lancet 1974: ii: 368-370.
165. Roghmann KJ, Tabloski PA, Bentley DW, Schiffman G. Immune response of elderly adults to Pneumococcus: variation by age, sex, and functional impairment. J Gerontol 1987: 42: 265-270.
166. Ross RD, Frengley JD. Elevated C-reactive protein in older people. J Am Geriatr Soc 1992: 40: 104-105.
167. Rowe JW, Kahn RL. Human aging: usual and successful Science 1987: 237: 143-149.
168. Russell MW, Prince SJ, Ligthart GJ, Mestecky J, Radl J. Comparison of salivary and serum antibodies to common environmental antigens in elderly, edentulous, and normal adult subjects. Aging Immunol Infect Dis 1990: 2: 275-286.
169. Russo CR, Schwab R, Weksler ME. Immune dysregulation associated with aging. Aging Immunol Infect Dis 1990: 3: 211-216.
170. Sanders ME, Makgoba MW, Sharrow SO, Stephany S, Springer TA, Young HA, Shaw S. Human memory T lymphocytes express increased levels of three cell adhesin molecules (LFA-3, CD2 and LFT-1) and three other molecules (UCHL1, CDW29 and Pyp-1) and have enhanced IFN gamma production. J Immunol 1988: 140: 1401-1407.
171. Sansoni P, Brianti V, Fagnoni F, Snelli G, Marcato A, Passeri G, Monti D, Cossarizza A, Franceschi C. NK cell activity and T-lymphocyte proliferation in healthy centenarians. Ann N Y Acad Sci 1992: 663: 250-261.
172. Sansoni P, Cossarizza A, Brianti V, Fagnomi F, Snelli G, Monti D, Marcato A, Passeri G, Ortolani C, Forti E, Fagiolo U, Passeri M, Franceschi C. Lymphocyte subsets and natural killer cell activity in healthy old people and centenarians. Blood 1993: 82: 2767-2773.
173. Santos MS, Meydani SN, Leka L, Wu D, Fotouhi N, Meydani M, Hennekens CH, Gaziano JM. Natural killer cell activity in elderly men is enhanced by beta-carotene supplementation. Am J Clin Nutr 1996: 64: 772-777.
174. Saririan K, Wali A, Almeida RP, Russo C. Increased serum HLA class I molecule levels in elderly human responders to influenza vaccination. Tissue Antigens 1993: 42: 9-13.
175. Schmucker DL, Daniels CK. Aging gastrointestinal infections and mucosal immunity. J Am Geriatr Soc 1985: 34: 377-384.
176. Schmucker DL, Heyworth MF, Owen RL, Daniels CK. Impact of aging on gastrointestinal mucosal immunity. Dig Dis Sci 1996: 41: 1183-1193.
177. Schwab R, Russo C, Weksler ME. Loss of MHC-restricted T cell recognition of influenza antigens in aging. Aging Immunol Infect Dis 1990: 3: 111-116.
178. Seres I, Csonger J, Mohacsi A, Leovey A, Fulop T. Age-dependent alterations of human recombination GM-CSF effects on human granulocytes Mech Ageing Dev 1993: 71: 143-154.
179. Shay K, Ship JA. The importance of oral health in the older patient. J Am Geriatr Soc 1995: 43: 1414-1422.
180. Shinkai S, Kohno H, Kimura K, Komura T, Asai H, Inai R Oka K, Kurokawa Y, Shephard R. Physical activity and immune senescence in men. Med Sci Sports Exerc 1995: 27: 1516-1526.
181. Shoham-Kesari H, Gershon H. Impaired reactivity to inflammatory stimuli of neutrophils from elderly donors. Aging Immunol Infect Dis 1992: 3: 169-183.
182. Smart BA, Rao KMK, Cohen HJ. Age-related increase in phorbol myristate acetate-induced lymphocyte adhesion to vascular endothelium. Mech Ageing Dev 1993: 72: 77-87.
183. Stadtman ER. Protein oxidation and aging. Science 1992: 257: 1220-1224.
184. Stein BE. Vaccinating elderly people. Protecting from avoidable disease. Drugs Aging 1994: 5: 242-253.
185. Steinmann GG. In: Müller-Hermelink HK, ed. The thymus: histophysiology and pathology. Heidelberg: Springer Verlag, 1984: 97.
186. Stitz L, Schmitz C, Binder D, Zindernagel R, Paoletti E, Becht H.
187. Stulnig TM, Buhler E, Bock G, Kirchebner C, Schonitzer D, Wick G. Altered switch in lipid composition during T cell blast transformation in the healthy elderly. J Gerontol A Biol Sci Med Sci 1995: 50A: B383-B390.
188. Sun WH, Brinkley N, Bidwell DW, Ershler WB. The influence of recombinant human interleukin-6 on blood and immune parameters in middle-aged and old rhesus monkeys. Lymphokine Cytokine Res 1993: 12: 449-455.
189. Suzuki T, Suzuki N, Daynes RA, Engleman EG. Dehydroepiandrosterone enhances IL-2 production and cytotoxic effector function of human T-cells. Clin Immunol Immunopathol 1991. 61: 202-211.
190. Taylor LD, Daniels CK, Schmucker DL. Does aging impair gastrointestinal mucosal immunity? Aging Immunol Infect Dis 1990: 3: 205-209.
191. Thiers BH, Maize JC, Spicer SS, Cantor AB. The effect of aging and chronic sun exposure on human Langerhans cell populations. J Invest Dermatol 1984: 82: 223-226.
192. Thoman ML. The pattern of T-lymphocyte differentiation is altered during thymic involution. Mech Ageing Dev 1995: 82: 155-170.
193. Thoman ML, Weigle WO. The cellular and subcellular bases of immunosenescence. Adv Immunol 1989: 46: 221-261.
194. Tosi P, Kraft R, Luzi P, Cinotorino M, Fankhauser G, Hess MW, Cottier H. Involution patterns of the human thymus. I. Size of the cortical area as a function of age. Clin Exp Immunol 1982. 47: 497-504.
195. Treanor J, Dumyati G, O'Brien D, Riley MA, Riley G, Erb S, Betts R. Evaluation of cold adapted reassortant influenza B virus vaccines in elderly and chronically ill adults. J Infect Dis 1994: 169: 402-407.
196. Tu KY, Matthews R, Matthews KS. Protective effect of vitamin E on lymphocyte growth capacity during incubation in vitro. Mech Ageing Dev 1995: 82: 129-148.
197. Ulmer JB, Donnerly JJ, Parker SE, Rhodes GM, Feigner PL, Dwark VJ, Gromkowski SH, Deck RR, Dewitt CM, Friedman A, Hawe LA, Leander KR, Martinez D, Perry HC, Shiver JW, Montgomery DL, Liu MA. Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 1993: 259: 1745-1748.
198. VanArkel C, Radl J. B cell lineage involvement in age-related monoclonal B cell proliferative disorders. Aging Immunol Infect Dis 1994: 5: 173-183.
199. VanDyke TE, Hoop GA. Neutrophil function and oral disease. Crit Rev Oral Biol Med 1990: 1: 117-133.
200. Villaneuva JL, Solana R, Alonso MC, Pena J. Changes in the expression of HLA-class II antigens on peripheral blood monocytes from aged humans. Dis Markers 1990: 8: 85-91.
201. Wayne SJ, Rhyne RL, Garry PJ, Goodwin JS. Cell-mediated immunity as a predictor of morbidity and mortality in subjects over 60. J Gerontol Med Sci 1990: 45: M45-M48.
202. Wei J, Xu H, Davies JL, Hemmings GR Increase of plasma IL-6 concentration with age in healthy subjects. Life Sci 1992: 51: 1953-1056.
203. Weigle WO, Chu EB. Age-related changes in the immune system and associated autoimmunity. Aging Immunol Infect Dis 1994: 5: 133-146.
204. Weksler ME. Immune senescence and adrenal steroids: immune dysregulation and the action of dehydroepiandrosterone (DHEA) in old animals. Eur J Clin Pharmacol 1993: 45: 21-23.
205. Wheeler TT, McArthur WP, Magnusson I, Marks RG, Smith J, Sarrett DC, Bender BS, Clark WB. Modeling the relationship between clinical, microbiologic, and immunologic parameters and alveolar bone levels in an elderly population. J Periodontol 1994: 65: 68-78.
206. Whisler RL, Beiqing L, Chen M. Age-related decreases in IL-2 production by human T cells are associated with impaired activation of nuclear transcriptional factors AP-1 and NF-AT. Cell Immunol 1996: 169: 185-195.
207. Whisler RL, Chen J-R, Newhouse YG. Identification of age-related changes in the activation/proliferation of human B cells independent from T cell influences. Aging Immunol Infect Dis 1990: 2: 82-90.
208. Whisler RL, Liu B, Wu LC, Chen M. Reduced activation of transcriptional factor AP-1 among peripheral blood T cells from elderly humans after PHA stimulation: restorative effect of phorbol diesters. Cell Immunol 1993: 152: 96-109.
209. Whisler RL, Newhouse YG. Function of T cells from elderly humans: Reduction of membrane events and proliferative responses mediated via T3 determinants and diminished elaboration of soluble T cell factors for B cell growth. Cell Immunol 1986: 99: 422-433.
210. Whisler RL, Newhouse YG, Bagenstose SE. Age-related reduction in the activation of mitogen-activated protein kinases p44mapk/ERK1 and p42mapk/ERK2 in human T cells stimulated via ligation of the T cell receptor complex. Cell Immunol 1996: 168: 201-210.
211. Whisler RL, Newhouse YG, Grants IS, Hackshow KV. Differential expression of the γ- and β-isoforms of protein kinase C in peripheral blood T and B cells from young and elderly adults. Mech Ageing Dev 1995: 77: 197-211.
212. Yang X, Stedra J, Cerny J. Repertoire diversity of antibody response to bacterial antigens in aged mice. IV. Study of VH and VL gene utilization in splenic antibody foci by in situ hybridization. J Immunol 1994: 152: 2214-2221.
213. Yen SS, Morales AJ, Khorram O. Replacement of DHEA in aging men and women. Potential remedial effects. Ann N Y Acad Sci 1995: 774: 128-142.
214. Zeng Y-X, Hirokawa K. Age change in signal transduction of T cells. Aging Immunol Infect Dis 1994: 5: 147-159.