1. CD45RA, CD8β, and IFNγ Are Potential Immune Biomarkers of Human Cognitive Function.
- Author
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Esgalhado AJ, Reste-Ferreira D, Albino SE, Sousa A, Amaral AP, Martinho A, Oliveira IT, Verde I, Lourenço O, Fonseca AM, Cardoso EM, and Arosa FA
- Subjects
- Cognitive Dysfunction epidemiology, Cognitive Dysfunction etiology, Cognitive Dysfunction metabolism, Humans, Immunophenotyping, Leukocytes, Mononuclear immunology, Leukocytes, Mononuclear metabolism, Lymphocyte Activation immunology, Prevalence, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, Biomarkers, CD8 Antigens metabolism, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, Cognition, Interferon-gamma metabolism, Leukocyte Common Antigens metabolism
- Abstract
There is increasing evidence that in humans the adaptive immunological system can influence cognitive functions of the brain. We have undertaken a comprehensive immunological analysis of lymphocyte and monocyte populations as well as of HLA molecules expression in a cohort of elderly volunteers (age range, 64-101) differing in their cognitive status. Hereby, we report on the identification of a novel signature in cognitively impaired elderly characterized by: (1) elevated percentages of CD8+ T effector-memory cells expressing high levels of the CD45RA phosphate receptor (Temra
hi ); (2) high percentages of CD8+ T cells expressing high levels of the CD8β chain (CD8βhi ); (3) augmented production of IFNγ by in vitro activated CD4+ T cells. Noteworthy, CD3+CD8+ Temrahi and CD3+CD8βhi cells were associated with impaired cognition. Cytomegalovirus seroprevalence showed that all volunteers studied but one were CMV positive. Finally, we show that some of these phenotypic and functional features are associated with an increased frequency of the HLA-B8 serotype, which belongs to the ancestral haplotype HLA-A1, Cw7, B8, DR3, DQ2, among cognitively impaired volunteers. To our knowledge, this is the first proof in humans linking the amount of cell surface CD45RA and CD8β chain expressed by CD8+ Temra cells, and the amount of IFNγ produced by in vitro activated CD4+ T cells, with impaired cognitive function in the elderly., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Esgalhado, Reste-Ferreira, Albino, Sousa, Amaral, Martinho, Oliveira, Verde, Lourenço, Fonseca, Cardoso and Arosa.)- Published
- 2020
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