Long-term cytomegalovirus infection leads to significant changes in the composition of the CD8+ T-cell repertoire, which may be the basis for an imbalance in the cytokine production profile in elderly persons.
In spite of the present belief that latent cytomegalovirus (CMV) infection drives CD8+ T-cell differentiation and induces premature immune senescence, no systematic studies have so far been performed to compare phenotypical and functional changes in the CD8+ T-cell repertoire in CMV-infected and noninfected persons of different age groups. In the present study, number, cytokine production, and growth potential of naive (CD45RA+ CD28+), memory (CD45RA- CD28+), and effector (CD45RA+ CD28- or CD45RA- CD28-) CD8+ T cells were analyzed in young, middle-aged, and elderly clinically healthy persons with a positive or negative CMV antibody serology. Numbers and functional properties of CMVpp65(495-503)-specific CD8+ T cells were also studied. We demonstrate that aging as well as CMV infection lead to a decrease in the size of the naive CD8+ T-cell pool but to an increase in the number of CD8+ effector T cells, which produce gamma interferon but lack substantial growth potential. The size of the CD8+ memory T-cell population, which grows well and produces interleukin-2 (IL-2) and IL-4, also increases with aging, but this increase is missing in CMV carriers. Life-long latent CMV infection seems thus to diminish the size of the naive and the early memory T-cell pool and to drive a Th1 polarization within the immune system. This can lead to a reduced diversity of CD8 responses and to chronic inflammatory processes which may be the basis of severe health problems in elderly persons.
Almanzar
Giovanni
G
Immunology Division, Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg, 10, A-6020 Innsbruck, Austria.
Schwaiger
Susanne
S
Jenewein
Brigitte
B
Keller
Michael
M
Herndler-Brandstetter
Dietmar
D
Würzner
Reinhard
R
Schönitzer
Diether
D
Grubeck-Loebenstein
Beatrix
B
D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology*; D000914:Antibodies, Viral / Q000097:blood; D018106:CD28 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005260:Female; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013997:Time Factors
D000914:Antibodies, Viral; D018106:CD28 Antigens; D016207:Cytokines; D017493:Leukocyte Common Antigens
Exp Gerontol. 2004 Apr;39(4):607-13
15050296
Emerg Infect Dis. 2001 Nov-Dec;7(6):945-51
11747720
Ann N Y Acad Sci. 1996 Jan 17;777:213-20
8624086
Vaccine. 2004 Jun 2;22(17-18):2103-5
15149765
Exp Gerontol. 2004 Apr;39(4):545-50
15050289
J Clin Microbiol. 1998 Sep;36(9):2434-8
9705369
Blood. 2003 Apr 1;101(7):2711-20
12433688
J Infect Dis. 1988 Aug;158(2):449-56
2841381
Nat Med. 2002 Apr;8(4):379-85
11927944
Curr Opin Immunol. 2000 Aug;12(4):390-6
10899017
Ann N Y Acad Sci. 2000 Jun;908:244-54
10911963
J Immunol. 2002 Jun 1;168(11):5455-64
12023339
J Virol. 2000 Sep;74(17):8140-50
10933725
Hum Immunol. 2004 May;65(5):416-22
15172440
Lancet Infect Dis. 2002 Nov;2(11):659-66
12409046
Vaccine. 2003 Sep 8;21(25-26):3826-36
12922116
J Immunol. 2002 Jun 1;168(11):5893-9
12023394
Neurosci Lett. 1997 Nov 28;238(1-2):17-20
9464644
Ann N Y Acad Sci. 2004 Jun;1019:123-6
15247004
Immunol Rev. 1997 Dec;160:31-42
9476663
Trends Immunol. 2001 Jun;22(6):293-5
11419409
J Infect Dis. 2000 Jan;181(1):165-75
10608763
Exp Gerontol. 2003 Sep;38(9):981-7
12954485
FASEB J. 1999 Jan;13(1):63-8
9872930
Clin Chim Acta. 2001 Aug 1;310(1):63-9
11485757
Trends Immunol. 2004 Aug;25(8):406-10
15275638
Lancet. 2001 Jul 14;358(9276):98-104
11463410
J Virol. 1999 Mar;73(3):2099-108
9971792
Drugs Today (Barc). 1998 May;34(5):409-13
15010704
J Immunol. 1999 Jun 15;162(12):7080-7
10358151
Hum Immunol. 2004 May;65(5):456-64
15172445
Hum Immunol. 2004 May;65(5):544-9
15172455
Immunol Today. 1996 Jun;17(6):267-72
8962629
J Immunol. 2003 Jan 1;170(1):613-9
12496450
Am J Pathol. 2004 Feb;164(2):589-600
14742264
Brain Res Brain Res Rev. 1995 Sep;21(2):195-218
8866675
J Immunol. 2002 Aug 15;169(4):1984-92
12165524
J Virol. 2001 Dec;75(24):12182-7
11711609
J Clin Immunol. 2000 Jul;20(4):250-6
10939712