Expansion of Tim-3⁺ CD4⁺ T cells in perinatally HIV-1-infected adolescents.

<p>(A) Flow dot plots show CD4⁺ T cell surface expression of CD28 and CD57 in perinatally HIV-1-infected children with shorter duration of HIV-1 infection (median: 11.2 y) and adolescents with longer duration of HIV infection (median:18.5 y). (B) Frequencies of CD28⁻, CD57⁺, and CD57⁺CD28⁻ CD4⁺ T cells in perinatally HIV-1-infected children and adolescents. (C) Flow dot plots show CD4⁺ T cell surface expression of PD-1 and Tim-3 in perinatally HIV-1-infected children with shorter duration of HIV infection (median: 11.2 y) and adolescents with longer duration of HIV-1 infection (median: 18.5 y). (D) Frequencies of Tim-3⁺, PD-1⁺, and PD-1⁺ Tim-3⁺CD4⁺ T cells in perinatally HIV-1-infected children and adolescents. A significant increase in Tim-3⁺CD4⁺ T cell (**p = 0.003) population was observed with age. P values were obtained using two-tailed Mann-Whitney <i>U</i> test. Flow dot plots are representative of all subjects in respective groups.</p

A positive correlation between Tim3⁺CD8⁺ T cells and HIV-1 plasma viral load (VL) in adolescents.

<p>Scatter plots showing correlation between HIV plasma viral load (VL) and Tim-3⁺CD8⁺ T cells (A and B), and PD-1⁺CD8⁺ T cells (C and D) in children (left) and adolescents (right) subjects. Tim-3⁺CD8⁺ T cells show a significant direct correlation with HIV-1 plasma viral load (VL) in adolescents (Spearman r = 0.74, *p = 0.017).</p

Numbers, CD4 count, viral load, CD8+ T cell activation, and age of subjects in each group.

<p>Numbers, CD4 count, viral load, CD8+ T cell activation, and age of subjects in each group.</p

Infection duration and age related decrease in CD8⁺ T cell activation in adolescents.

<p>(A) Flow dot plots show CD8 surface expression of CD38 and HLA-DR in perinatally HIV-1 infected children (median: 11.2 y) and adolescents (median: 18.5 y). Dot plots are representative of all subjects in respective groups. (B) Frequencies of HLA-DR⁺CD38⁺CD8⁺ T cells and CD38⁺CD8⁺ T cells in perinatally HIV-1-infected children and adolescents. A significant decrease in CD38⁺CD8⁺ T cell (*p = 0.016) and a marginal decrease in HLA-DR⁺CD38⁺CD8⁺ T cell (p = 0.103) populations were observed with the duration of HIV infection. P values were obtained using two-tailed Mann-Whitney <i>U</i> test.</p

PD-1⁺CD8⁺ T cells have a strong significant correlation with immune activation in both age groups.

<p>Scatter plots showing a correlation between immune activation and PD-1⁺ or Tim3⁺CD8⁺ T cells. (A) and (B) show a significant strong correlation between HLA-DR⁺CD38⁺CD8⁺ T cell and PD-1⁺CD8⁺ T cells in children with shorter duration of HIV-1 infection (Spearman r = 0.947, **p = 0.004) and adolescents with longer duration of HIV-1 infection (Spearman r = 0.70, *p = 0.026) respectively. (C) and (D) show a correlation between HLA-DR⁺CD38⁺ CD8⁺ T cells and Tim-3⁺CD8⁺ T cells in both age groups.</p

Subject characteristics.

<p>R/E = Race/Ethnicity, W/H = White/Hispanic, B/NH = Black/Non-Hispanic,</p>§<p>ART = Antiretroviral treatment, ZDV = Zidovudine, 3TC = Lamivudine (2′, 3′-dideoxy-3′-thiacytidine), ABC = Abcavir, TDF = Tenofovir disoproxil fumarate, ATV/r = Atazanavir/ritonavir, LPV/r = Lopinavir/ritonavir, ddI = Didanosine, EFV = Efavirenz.</p

Association between CD57 expression on CD4 T cells and disease progression.

<p><b>A.</b> Comparison of CD57 expression on CD4 T cells between progression groups. <b>B.</b> Correlation between log viral load (LVL) and CD57 expression on CD4 T cells. <b>C.</b> Correlation between CD4% and expression of CD57 on CD4 T cells.</p

Patient cohort characteristics.

a<p>Log viral load.</p>b<p>H = Hispanic; AA = African American.</p

Comparison of cytokine secretion of HIV-1 Gag specific CD8+ T cells between progression groups.

<p>Secretion of single cytokines is shown in panel A. Functional profile of HIV-1 Gag specific CD8+ T cells is shown in panel B. (+) denotes a positive response for that particular cytokine. Gray bars represent NS subjects and black bars represent SS subjects. The solid bars represent the mean and the error bars represent the standard error of the mean.</p

Categorization of subjects into two distinct disease progression groups.

<p>Two examples of representative patients categorized into either long-term survivors with No Immune Suppression (NS) (A) or Severe Immune Suppression (SS) (B). The dotted line is the boundary of the CD4% value of that progression group. The shading shows the window from within which PBMC samples were chosen for study.</p