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.
Leng
Qibin
Q
Ruth Ben-Ari Institute of Clinical Immunology and AIDS Center, Kaplan Medical Center, Hebrew University Hadassah Medical School, 76100, Rehovot, Israel.
Bentwich
Zvi
Z
Borkow
Gadi
G
D000069594:Abatacept; D000375:Aging / Q000276:immunology*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology; D060908:CTLA-4 Antigen; D006801:Humans; D018796:Immunoconjugates; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D000069594:Abatacept