Figure 1.
CHS All Stars elders display classic features of aging in the T cell compartment.
By multicolor flow cytometry, CD3+ TCRαβ T cells in PBMC were examined for senescence-associated loss of expression of the costimulatory receptor CD28, and gains of expression of the adhesion molecule CD57 and the prototypic NKR CD56, as well as the expression of senescence antigens p16, p53, pRB, and γH2AX. (A) Scatter plot of the frequencies of CD28null and CD57+ cells in the CD4 and CD8 T cell compartments. (B) Representative profiles of p16, p53, pRB, and γH2AX expression in CD4 and CD8 T cells. (C) Scatter plot of the frequencies of CD28null and CD56+ T cells. (D, E, F) Scatter plot of the levels of expression of CD56 and CD57 measured as cell frequencies (D), as MFI (E), and as GMFI (F) in the CD4 and CD8 T cell compartments. Solid and dashed lines represent significant and non-significant regression lines, respectively, with the indicated R2 and p-values.
Table 1.
Demographic and health characteristics of functional categories of CHS All Stars elders.
Figure 2.
Group assignment of CHS All Stars elders based on 3MSE/ADL scores is discriminated by physical and immune parameters.
Discriminant function analysis was performed on collated physical, demographic, and immunological data (see Table 1 and Tables S1, S2, S3, S4). Using all variables, both simple and stepwise models showed significant separation between impaired and unimpaired groups around the centroid, indicated as the zero-mark on the x-axis (A). Using only immune variables (B), or T cell subset frequency (C), or receptor density on T cells (D) stepwise models showed significant separation between the two groups despite some overlap. When humoral factors were used only in the analysis, only a simple linear model could be constructed (E). Significant contributing variables to models shown in B, C, D were: gait speed (GS); the T cell subsets CD4+CD56+ (46), CD4+CD28nullCD56+CD57+ (4678), CD8+CD158e+ (8e), CD8+CD56+ (86), and CD8+CD28nullCD57+ (878); GMFI of CD57 on CD4 T cells (47 g); the GMFI of NKG2D (8 Dg) and NKG2A (8 Ag) on CD8 T cells; the GMFI (N6 g) and MFI (N6 m) of CD56 on DN T cells; the MFI of NKG2D on CD8 T cells (8 Dm); and the humoral factors GMCSF (GF), IFN-γ (IF), IL-6 (L6), and IL-12p70 (L12). The indicated p-values were based on χ2 test of Wilk's lambda discriminant statistic.
Table 2.
T cell and cytokine profiles of unimpaired and impaired elders.
Table 3.
T cell and humoral predictors of “Unimpaired” phenotype.
Figure 3.
NKRs CD56 and NKG2D expressed on T cells are competent receptors that induce activation of T cells independent of TCR-derived signals.
Induction of cell surface expression of activation antigens (A) CD25 and (B) CD69, markers of granule exocytosis (C) CD107a and (D) CD107b; and of cytoplasmic stores of (E) cytolytic proteins (combined staining for perforin and granzyme), and the cytokines (F) IL-4 (G) IL-17, and (H) IFN-γ in CD4 and CD8 T cells in response to 24-hr incubation in anti-TCRαβ, or anti-CD56, or anti-NKG2D, or recombinant NKG2D ligands MIC-A, ULPB-1, ULPB-2, and ULPB-3. Data shown are means (box) and standard deviations (whiskers) from 13-17 randomly selected unimpaired subjects. P-values of all of the measured cellular responses were significant (p<0.05, Kruskall-Wallis analysis of variance).