Comparison of endemic normal children (ENCh) and filarial-infected children (InfCh).

<p>A) Total effector∶effector memory ratios in CD4⁺ cells (left panel) and CD8⁺ cells (right panel). Values were calculated for each patient using the percentages of either CD45RA⁺ or CD45RA⁻ cells and ratios were derived using the following equation: (% T_TermEff+% T_EFF)/(% T_EMRA⁺+% T_EM). B) Geometric mean fluorescence intensity (GMFI) of IL-7Rα expression in T_EMRA⁺ cells (left panels), T_CM cells (middle panels), and T_EM cells (right panels) for CD4⁺ cells (top panels) and CD8⁺ cells (bottom panels). Each point represents an individual patient and the horizontal lines represent geometric means; the Mann-Whitney U test was used to derive p-values.</p

Mechanism of immune modulation caused by helminth infections affecting immune responses and susceptibility to TB.

<p>Exposure to helminth infection occurs early in areas of endemicity, with early mixed Th1/Th2 responses eventually leading to expansion of Th2 and Treg responses with establishment of chronic infection. This in turn can alter the phenotype and functionality of antigen-presenting cells as shown. The immune skewing that occurs as a result alters immune responses to <i>Mtb</i> and might affect susceptibility to TB. In utero sensitization to helminth antigens that leads to a similar skewing of the neonatal immune system can occur and thereby alter the immunogenicity of <i>Mtb</i>-specific vaccines.</p

HLA-DR expression on Effector Cells.

<p>Values are the geometric mean (range) of HLA-DR expressing cells for each patient group for CD4⁺ and CD8⁺ effector cells. HLA-DR⁺ expression was determined as a % of CCR7⁻CD27⁻ cells within either the CD45RA⁺ compartment (Terminal Effector Cells) or CD45RA⁻ compartment (Effector Cells).</p><p>EN – Endemic Normal; Inf – Filarial-infected; CLInf – Cleared Infected; ENCh – Uninfected Children; InfCh – Filarial-infected Children.</p>a<p>Indicates a significant difference between EN and Inf.</p>b<p>Indicates a significant difference between EN and CLInf.</p

Geometric mean % size of each T cell subset relative to all 6 cell phenotypes.

<p>The percent of each cell population for the CD45RA⁺ cells (including naïve, T_EMRA⁺, and T_TermEff; A, B, and C in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0019197#pone-0019197-g001" target="_blank">Fig. 1</a> respectively) and the CD45RA⁻ cells (including T_CM, T_EM, and T_EFF; D, E, and F in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0019197#pone-0019197-g001" target="_blank">Fig. 1</a> respectively) was calculated for a given patient and the % contribution of each population relative to the six total populations was then determined. The geometric mean percent of each cell phenotype (compartment) for each patient group was then calculated based upon the percentages derived from all of the patients within a group. Ranges for each category are shown in parentheses.</p><p>EN – Endemic Normal; Inf – Filarial-infected; CLInf – Cleared Infected; ENCh – Uninfected Children; InfCh – Filarial-infected Children.</p

Geometric mean fluorescence intensity (GMFI) of IL7-Rα expression.

<p>GMFI of IL-7Rα is shown for EN, Inf, and CLInf patients for T_EMRA⁺ cells (top panels) and T_EM cells (bottom panels) in CD4⁺ cells (left panels) and in CD8⁺ cells (right panels). Each point represents an individual patient and the horizontal lines represent geometric means; the Mann-Whitney U test was used to derive p-values.</p

IL-7 and soluble IL-7Rα in patient sera.

<p>A) IL-7 (left panel) and soluble IL-7Rα (sCD127; right panel) levels as measured in the sera of patients from all 5 patient groups. B) Correlation between sCD127 levels in the sera and geometric mean fluorescence intensity (GMFI) of IL-7Rα expression on CD4⁺ T_CM cells (as measured by flow cytometry).</p

Total T_EFF and T_EM cells.

<p>Data for T_EFF (left panels) and T_EM (middle panels) cells are expressed as a % of CD4⁺CD45RA⁻ cells (top panels) and CD8⁺CD45RA⁻ cells (bottom panels) in EN, Inf, and CLInf patients. The right panels display the T_EFF to T_EM ratio for each patient using values derived from percentages of CD45RA⁻ cells for each T cell subset. Each point represents an individual patient and the horizontal lines represent geometric means; the Mann-Whitney U test was used to derive p-values.</p

Patient Groups.

<p>Patient groups from the filarial-endemic island of Mauke in the Cook Islands. Filarial infection status was determined at two timepoints (1975 and 1992); age is shown as the range and mean for each group of patients.</p>a<p>All patients positive for infection were microfilaremic; negative status indicates a negative test for circulating antigen (CAg) and microfilaremia.</p><p>N/A – Not applicable.</p

Total CD45RA⁺ and CD45RA⁻ cells.

<p>Data for CD45RA⁺ (top panels) and CD45RA⁻ (bottom panels) cells are expressed as a percent of viable CD3⁺ cells in endemic normals (EN), filarial-infected patients (Inf), and in patients who had cleared their filarial infection (CLInf) for CD4⁺ cells (left panels) and CD8⁺ cells (right panels). Each point represents an individual patient and horizontal lines represent geometric means.</p

T cell populations in the CD3⁺CD4⁻CD8⁻ compartment.

<p>A) Total CD4⁻CD8⁻ cells expressed as a % of CD45RA⁺ cells (left panel) and CD45RA⁻ cells (right panel) in all 5 patient groups. B) Effector∶Effector memory ratios in adult patient groups for CD45RA⁺ cells (% T_TermEff/% T_EMRA⁺; left panel) and CD45RA⁻ cells (% T_EFF/% T_EM; right panel). Each point represents an individual patient and the horizontal lines represent geometric means; the Mann-Whitney U test was used to derive p-values.</p