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- IL-15 induces CD8+ T cells to acquire functional NK receptors capable of modulating cytotoxicity and cytokine secretionPublication . Correia, Margareta P.; Costa, Alexandra V.; Uhrberg, Markus; Cardoso, Elsa M.; Arosa, FADuring the last years several authors have described a small population of CD8+ T cells expressing NK receptors (NKRs). Although their origin remains largely unknown, we have recently demonstrated that IL-15 is capable of inducing NKR expression in purified human CD8+CD56− T cells. In this study we show that IL-15-driven NKR induction in CD8+ T cells was linked with CD56 de novo acquisition, consistent with an effector-memory phenotype, increased anti-apoptotic levels, high granzyme B/perforin expression and with the ability of displaying in vitro NK-like cytotoxicity. Interestingly, dissection of NKR functional outcome in IL-15-cultured CD8+ T cells revealed: (i) that NKG2D cross-linking was able per se to upregulate degranulation levels and (ii) that KIR and NKG2A cross-linking upregulated secretion of cytokines such as IFN-, TNF-, IL-1 and IL-10. These results suggest that IL-15 is capable of differentiating CD8+ T cells into NK-like T cells displaying a regulatory phenotype.
- HLA‐A23/HLA‐A24 serotypes and dementia interaction in the elderly: Association with increased soluble HLA class I molecules in plasmaPublication . Cardoso, Elsa M.; Gomes, Vânia Lourenço; Esgalhado, André J.; Ferreira, Débora Reste; Oliveira, Nádia; Amaral, Ana Saraiva; Martinho, António; Gama, Jorge; Verde, Ignacio; Lourenço, Olga; Fonseca, Ana C.; Buchli, Rico; Arosa, Fernando A.MHC class I molecules regulate brain development and plasticity in mice and HLA class I molecules are associated with brain disorders in humans. We investigated the relationship between plasma-derived soluble human HLA class I molecules (sHLA class I), HLA class I serotypes and dementia. A cohort of HLA class I serotyped elderly subjects with no dementia/predementia (NpD, n = 28), or with dementia (D, n = 28) was studied. Multivariate analysis was used to examine the influence of dementia and HLA class I serotype on sHLA class I levels, and to compare sHLA class I within four groups according to the presence or absence of HLA-A23/A24 and dementia. HLA-A23/A24 and dementia, but not age, significantly influenced the level of sHLA class I. Importantly, the concurrent presence of HLA-A23/A24 and dementia was associated with higher levels of sHLA class I (p < 0.001). This study has shown that the simultaneous presence of HLA-A23/HLA-A24 and dementia is associated with high levels of serum sHLA class I molecules. Thus, sHLA class I could be considered a biomarker of neurodegeneration in certain HLA class I carriers.
- CD45RA, CD8β, and IFNγ Are Potential Immune Biomarkers of Human Cognitive FunctionPublication . Esgalhado, AJ; Reste-Ferreira, Débora; Albino, Stephanie; Sousa, Adriana; Amaral, Ana Paula; Martinho, António; Oliveira, Isabel Tomás; Verde, Ignacio; Lourenço, Olga; Fonseca, Ana M; Cardoso, Elsa M.; Arosa, FAThere 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+ Temra hi 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.