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

Comparison of differentiation profiles of Gag specific effector CD8+ T cells between progression groups.

<p>All Gag specific responses are shown in panel A. Only immuodominant responses (the response with the highest magnitude for each individual) are shown in panel B. The line in each column represents the median value. The differentiation phenotype is referenced beneath each column.</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

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

Areas of Gag targeted by CD8+ T cell responses.

<p>The frequency of recognition of individual single peptides are shown for the total cohort in panel A. The NIH AIDS Reagent peptides for HIV-1 Gag are represented by their peptide number. A comparison of the frequency of recognition of single peptides between the two progression groups is shown in panel B. The percentage of each group responding to 6 of the individual Gag peptides is shown in panel C.</p

Comparison of differentiation profiles of total CD4 T cells between progression groups.

<p>We used expression of CCR7 and CD45RA to categorize CD4 T cells into one of four differentiation phenotypes. Filled circles (•) represent LTS-SS patients and empty circles (○) represent LTS-NS patients. The line in each column represents the median and the differentiation phenotype is beneath each column.</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

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

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