CTLA-4 upregulation during aging

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. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.