Journal Article

CD45RA, CD8β, and IFNγ Are Potential Immune Biomarkers of Human Cognitive Function

Fonseca, Ana M., Amaral, Ana Paula, Martinho, António, Albino, Stephanie E., Verde, Ignacio, Sousa, Adriana, Cardoso, Elsa M., Reste-Ferreira, Débora, Lourenço, Olga, Esgalhado, André J., Oliveira, Isabel T., Arosa, Fernando A.

2020

Overview

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 (T emra hi ); (2) high percentages of CD8+ T cells expressing high levels of the CD8β chain (CD8β hi ); (3) augmented production of IFNγ by in vitro activated CD4+ T cells. Noteworthy, CD3+CD8+ T emra hi and CD3+CD8β 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 CD8β chain expressed by CD8+ T emra cells, and the amount of IFNγ produced by in vitro activated CD4+ T cells, with impaired cognitive function in the elderly.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Aging / Biomarkers / Brain / brain cognition / CD3 antigen / CD4 antigen / CD4+ IFNγ / CD45RA antigen / CD8 antigen / CD8 Antigens - metabolism / CD8-Positive T-Lymphocytes - immunology / CD8-Positive T-Lymphocytes - metabolism / Cell surface / Cerebrospinal fluid / Cognition / Cognitive ability / Cognitive Dysfunction - epidemiology / Cognitive Dysfunction - etiology / Cognitive Dysfunction - metabolism / Cytokines / Cytomegalovirus / Effector cells / effector-memory CD8+ T cells / elderly / Exercise / Females / Haplotypes / healthy aging / Histocompatibility antigen HLA / HLA class I / Homeostasis / Humans / Immunology / Immunophenotyping / Interferon-gamma - metabolism / Leukocyte Common Antigens - metabolism / Leukocytes, Mononuclear - immunology / Leukocytes, Mononuclear - metabolism / Lymphocyte Activation - immunology / Lymphocytes / Lymphocytes T / Males / Memory / Memory cells / Monocytes / Older people / Prevalence / Serology / Software / T-Lymphocyte Subsets - immunology / T-Lymphocyte Subsets - metabolism / γ-Interferon