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.
The dramatic decline in immune function with age, especially in T cell proliferative activity, has been documented extensively in experimental animal models and in clinical studies of the elderly. A similar proliferative decline is also seen in long-term T lymphocyte cultures used to study in vitro cellular senescence. We have compared the peripheral blood T lymphocytes of centenarians and younger controls for the cell surface expression of CD28, a costimulatory molecule that is required for optimal activation and proliferation following engagement of the T cell receptor. Our analysis shows a significant decrease (p < 0.001) in the percentage of T cells expressing CD28 in the elderly cohort, with values ranging from 44% to 90%, as compared to the mean control value of 91%. The decline in the percentage of CD28+ T cells correlates with a reduction in the CD4/CD8 ratio (r2 = 0.695, p < 0.0001). Concommitantly, experiments using an in vitro T cell culture system showed a progressive loss of CD28 expression with culture "age." The concordance of proliferative decline and loss of CD28 in the centenarians and in the in vitro cultures suggest that a Hayflick phenomenon may operate in vivo leading to immunosenescence.
Effros
R B
RB
Department of Pathology and Laboratory Medicine, UCLA School of Medicine 90024, USA.
Boucher
N
N
Porter
V
V
Zhu
X
X
Spaulding
C
C
Walford
R L
RL
Kronenberg
M
M
Cohen
D
D
Schächter
F
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018106:CD28 Antigens / Q000097:blood*; D016022:Case-Control Studies; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000276:immunology; D006801:Humans; D016014:Linear Models; D018655:Lymphocyte Count; D008875:Middle Aged; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000276:immunology*
D018106:CD28 Antigens