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

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 (Temrahi); (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.

HLA‐A23/HLA‐A24 serotypes and dementia interaction in the elderly: Association with increased soluble HLA class I molecules in plasma

“…However, and paraphrasing Kessler et al, 22 characterization of specific HLA‐A, HLA‐B and HLA‐C types will be crucial to optimally exploit the diagnostic value of sHLA class I molecules in dementia. On the other hand, the fact that 55 out of 56 elderly subjects were CMV seropositive points against the possibility that the differences found in the level of sHLA class I might have been caused by CMV infection, as previously reported for other immunological variables 29 . Conclusively, our findings provide a first insight into a new phenomenon but raises important questions to be answered.…”

“…28 The elderly subjects under study were initially classified into three discrete groups, as previously described. 29 The first group included the elderly without cognitive impairment (NCI, n = 13, GDS stages 1/2, ACE-R values indicative of the absence of cognitive impairment, that is, 106.49 ± 3.05% of the minimal normal score, and without clinical evidence of disease with cognitive impairment). The second group included elders with mild cognitive impairment (MCI, n = 15, GDS stage 3, and ACE-R values slightly lower than the minimal considered as normal, that is, 73.6 ± 3.61% of the minimal normal cognitive impairment level).…”

“…All subjects under study were characterized for HLA class I serotype as previously described. 29 Briefly, DNA was extracted from peripheral blood using the MagAttract ® DNA Blood Midi M48 kit or QIAamp DNA Stool Mini Kit (QS). HLA typing was accomplished using One Lambda ® LABTypeSSO kits at low resolution level (serology equivalent) for HLA-A, -B, -C, -DRB1, -DQA1, and -DQB1 loci followed by Luminex ® xMAP ® technology.…”

“…All subjects under study were characterized for Cytomegalovirus (CMV) seropositivity as previously described. 29 Briefly, cryopreserved plasma samples were thawed and anti-CMV IgG antibodies detected by using 96-well microplate ELISA kits (Demeditec), according to manufacturer instructions. Tests were performed in duplicate, and the amount of CMV-specific IgG antibody bound calculated using a BioRad xMark™ Microplate Absorbance Spectrophotometer.…”

Open MHC Class I Conformers: A Look through the Looking Glass

“…The study of the effect of the expression of open HLA-I conformers in these two areas of knowledge is relatively uncharted territory. However, the existence of close connections between HLA-I molecules and IR-mediated signaling [ 51 , 134 ], progression of cancer [ 83 , 84 , 85 , 86 , 87 , 122 , 123 , 124 , 125 , 126 ] and development of cognitive disorders [ 207 , 208 , 209 , 210 , 211 , 212 ] is substantial grounds to keep clearing the way towards a better understanding of the original function of MHC-I molecules [ 6 , 7 , 8 , 9 ].…”