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Mech Ageing Dev. 2002 Jul;123(10):1419-21.

CTLA-4 upregulation during aging.

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Ruth Ben-Ari Institute of Clinical Immunology and AIDS Center, Kaplan Medical Center, Hebrew University Hadassah Medical School, 76100, Rehovot, Israel.


The immune system gradually becomes anergic with age. Here, we measured intracellular levels of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), a negative regulator of T-cells, in 53 healthy individuals aged 18-94. We found a highly significant correlation between age and percent of CTLA-4+CD4+ cells (r=0.6, P<0.001) and between age and mean fluorescence intensities of CTLA-4 (i.e. number of molecules, r=0.61, P<0.001). CTLA-4 levels were also correlated with immune activation, determined by levels of HLA-DR+CD3+ cells (r=0.55, P<0.001). We postulate that immune senescence associated with age is caused in part by chronic immune activation with related decrease in CD28 costimulatory molecules and increase in inhibitory CTLA-4 molecules.

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