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

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

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

Total T cell activation was not influenced by exposure.

<p>The expression level of activation markers CD38 and HLA-DR were compared between VP group (squares, n = 6) and NVP group (circles, n = 10). The expression of CD38 on total CD4⁺ (A) and total CD8⁺ (B) T cells showed no significant difference. No significant difference was seen in CD4⁺ T cell co-expression of CD38 and HLA-DR (C). However, CD8⁺ T cells from the VP group co-expressed significantly higher of CD38 and HLA-DR compared to the NVP group (denoted by *) (D).</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

Clinical parameters of each study group.

<p>Clinical parameters of each study group.</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

Clinical data of 8 individuals from VPG at time point 0 and 1 year later at time point 1.

*<p>indicates that the individuals partner started to receive anti-retroviral therapy after time point 0, and had a viral load below 50 copies per ml.</p

Direction of exposure and T cell IFN-γ response correlations.

<p>IFN-γ T cell responses from the viremic partner (VP) group were plotted against the corresponding average number of unprotected receptive (A) or insertive (B) anal exposures to a partner's HIV-1. Significant correlations (denoted by *) were determined by two-tailed nonparametric spearmans correlation, spearman r (r), and linear regression analysis was plotted as straight lines.</p