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.
Although it is generally recognized that the function of the immune system declines with age, the nature of the underlying defects is still poorly understood. We now demonstrate the predominance of CD8(+)CD28(-) T cell clonal expansions in elderly persons who fail to produce specific Abs following influenza vaccination. These clones express effector cell markers and are mostly CD45RA(+). When isolated and put into culture, they are unable to proliferate, but produce IFN-gamma (but no IL-5) upon stimulation with anti-CD3 or autoantigen. These autoreactive CD8(+) type 1 effector cells seem to trigger a Th1 polarization, as CD4(+) T cells from elderly persons without in vivo Ab production produce Th1, but only low amounts of Th2 cytokines upon in vitro stimulation with PHA. Therefore, the increased occurrence of CD8(+)CD28(-) clonal expansions may be decisive for the development of immune deficiency in the elderly.
Saurwein-Teissl
Maria
M
Institute for Biomedical Aging Research of the Austrian Academy of Sciences, Central Institute for Blood Transfusion, University Clinics Innsbruck, Innsbruck, Austria.
Lung
Thomas L
TL
Marx
Florentine
F
Gschösser
Claudio
C
Asch
Esther
E
Blasko
Imrich
I
Parson
Walther
W
Böck
Günther
G
Schönitzer
Diether
D
Trannoy
Emanuelle
E
Grubeck-Loebenstein
Beatrix
B
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D000914:Antibodies, Viral / Q000097:blood*; D018106:CD28 Antigens / Q000032:analysis*; D016827:CD8 Antigens / Q000032:analysis*; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007252:Influenza Vaccines / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014611:Vaccination
D000914:Antibodies, Viral; D018106:CD28 Antigens; D016827:CD8 Antigens; D016207:Cytokines; D007252:Influenza Vaccines