Cd45ra, Cd8 Beta, And Ifn Gamma Are Potential Immune Biomarkers Of Human Cognitive Function

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 CD8 beta chain (CD8 beta(hi)); (3) augmented production of IFN gamma by in vitro activated CD4+ T cells. Noteworthy, CD3+CD8+ Temra (hi) and CD3+CD8 beta(hi) 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 CD8 beta chain expressed by CD8+ Temra cells, and the amount of IFN gamma produced by in vitro activated CD4+ T cells, with impaired cognitive function in the elderly.