Modulation of CD38 expression in human longevity: A flow cytometric study

The dynamics of CD38 expression innewborns and young healthy donors hasbeen widely investigated for many years.However, little is known about the modulationof this marker during humanageing. We analyzed the changes inCD38 expression in peripheral bloodlymphocytes (PBL) from subjects whowere centenarians. For this purpose weused polychromatic flow cytometry, apowerful technology that allows the determinationof multiple antigens (in ourcase, up to 8) present in the same cell.Among the subsets within CD4+ andCD8+ T cell populations identified bythis approach, we investigated the expressionof CD38 together with markersrelated to extrathymic T cell differentiation(CD45RA and CCR7), T cell survival(CD127/IL-7rα) and activation/apoptosis(CD95). The groups analysed includedyoung donors (21±2 years old),middle-aged individuals (60±1.5 yearsold) and centenarians.By automatic boolean gating, we identifiedall the possible subsets obtained bythe combination of positive and negativeexpression for each marker indicatedabove. Moreover, we could distinguish betweendim or bright expression of CD38.CD38 expressed by CD4+ T cells doesnot show significant modifications in thethree samples either in of the virgin ormemory subsets.A slight increase in CD38 expressionwas found in PBL CD8+ T cells from centenarians.These CD8+/38dim T cells displayeda CD45RA-/CCR7+ central memoryor CD45RA-/CCR7- effector memoryphenotype. Further, CD38 expressionwas associated with the presence ofCD95 and the absence of CD127/IL-7rα.These results were also confirmed byCluster Analysis (CA) and PrincipalComponent Analysis (PCA) of the highnumber of T cell populations identifiedby flow cytometry. These bioinformatictechniques cluster the individuals accordingto the flow cytometric profile,which confirmed that the subsets with anincreased expression of CD38 (CD38bright) are more frequent in the sampleof centenarians.In conclusion, our data indicate amodulation of CD38 expression in CD8+T cells during human ageing. In particular,the preferential coexpression of thisantigen with CD95 but not CD127/IL-7r_suggests an age-dependent acquisition ofan effector phenotype of CD8+ T cellswhich could, at least in part, explain thechronic pro-inflammatory status presentin centenarians.