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Results: 6

1.
Figure 3

Figure 3. From: IL-15 delays suppression and fails to promote immune reconstitution in virally suppressed chronically SIV-infected macaques.

IL-15 fails to promote CD4+ T-cell recovery in peripheral tissues despite the induction of local proliferation. (A) Percent Ki-67+ among memory (CD95+) CD4+ T cells and (B) percent of total CD4+ T cells in the lymphocyte gate in the ILN, BAL, and jejunum at pretherapy (d−13) and at d28 after therapy initiation. (C) Percent CCR5+ CD4+ memory T cells in the BAL at the same time points after therapy initiation. In panels A and C, data are expressed as in Figure 1B. In panel B, each line represents an animal.

Enrico Lugli, et al. Blood. 2011 September 1;118(9):2520-2529.
2.
Figure 2

Figure 2. From: IL-15 delays suppression and fails to promote immune reconstitution in virally suppressed chronically SIV-infected macaques.

Absence of proliferation and expansion of selective CD4+ T-cell memory subsets by IL-15. (A) Fold change in CD4+ and CD8+ TCM, TTM, and TEM absolute counts and (B) percent of Ki-67+ cells in the same T-cell subsets in the peripheral blood during treatment with IL-15, ART, or ART+IL-15. The horizontal gray line indicates no change versus baseline. #P < .05 vs d−7; Wilcoxon rank-sum test. The color of each “#” symbol refers to the group whose distribution is significantly different from the reference group. Data are expressed as in Figure 1B. In Figure 1C, individual animals are not shown.

Enrico Lugli, et al. Blood. 2011 September 1;118(9):2520-2529.
3.
Figure 1

Figure 1. From: IL-15 delays suppression and fails to promote immune reconstitution in virally suppressed chronically SIV-infected macaques.

Suppression of viral replication and CD8+ T-cell activation do not favor IL-15–induced CD4+ T-cell expansion. (A) Plasma SIV RNA copies at different days after introduction (gray box) or cessation of therapies. Each line represents a different animal. (B) Fold change in HLA-DR+CD8+ T cells after treatment initiation versus baseline (d−7) in TCM, TTM, and TEM cells. Bars show the interquartile range, and the wide bar shows the median, of the distribution. Each point represents an animal. (C) Fold change in CD4+ and CD8+ absolute T-cell counts in the peripheral blood in the different treatment groups. Data are expressed as in panel B. The horizontal gray line indicates no change versus baseline. #P < .05 vs ART; Wilcoxon rank-sum test.

Enrico Lugli, et al. Blood. 2011 September 1;118(9):2520-2529.
4.
Figure 4

Figure 4. From: IL-15 delays suppression and fails to promote immune reconstitution in virally suppressed chronically SIV-infected macaques.

IL-15 mediates the expansion of antigen-specific CD8+ but not CD4+ T cells. (A) Percent Ki-67+ SIV-specific (Gag and Nef averaged) and CMV-specific CD4+ T-cells and (B) CD8+ T cells before and after therapy introduction. N/A indicates data not available because of low number of responding cells. Data are expressed as in Figure 2B. #P < .05 vs ART; Wilcoxon rank-sum test. (C) Percent of Gag-, Env-, or CMV-specific CD4+ (top) and CD8+ (bottom) T cells producing cytokines (IL-2 or TNF-α or IFN-γ) in the different treatment groups in the peripheral blood at d−7 or at d46 after therapy initiation. Data are expressed as in Figure 1B. (D) As in panel C but in the ILN and the BAL at baseline (“pre”) and at d28. Data from the jejunum are not depicted because very low responses were detected.

Enrico Lugli, et al. Blood. 2011 September 1;118(9):2520-2529.
5.
Figure 5

Figure 5. From: IL-15 delays suppression and fails to promote immune reconstitution in virally suppressed chronically SIV-infected macaques.

IL-15 allows the induction of IL-2-producing SIV-specific CD4+ T cells under ART but does not improve antigen-specific CD8+ T-cell function. (A) Representative example of the expression of IFN-γ, IL-2, and TNF-a in response to Gag peptide pool at d−7 and at d46 after therapy initiation. Numbers indicate the percentage of cells in the quadrants. (B) Pie charts and bars representing the quality of the SIV-specific (Gag and Env averaged) CD4+ T-cell response at baseline and at d46 after ART treatment. Each section of the pie chart represents a specific combination of cytokines, as indicated by the color at the bottom of the bar graph. Data were expressed as in Figure 2B. #P < .05 vs d−7; Wilcoxon rank-sum test. (C) As in panel B but in the different treatment groups at d46 after treatment initiation. #P < .05 vs IL-15; Wilcoxon rank-sum test. (D) Percentage of SIV-specific (Gag and Env averaged) CD4+ T-cells with TCM, TTM, or TEM cell phenotype of total memory cells at d−7 and at d46 after treatment initiation. Data are expressed as in Figure 1B.

Enrico Lugli, et al. Blood. 2011 September 1;118(9):2520-2529.
6.
Figure 6

Figure 6. From: IL-15 delays suppression and fails to promote immune reconstitution in virally suppressed chronically SIV-infected macaques.

Post treatment effects of IL-15 therapy. (A) Fold change in the absolute count of total CD4+ T cells in the peripheral blood at d59 (d13 posttherapy interruption) in the ART and ART+IL-15 groups. Each point represents an animal. The median ± SEM is depicted. (B) Representative example of the expression of phosphatidylserine on the cell surface by d59 TEM CD4+ T cells after overnight culture. (C) Summary of the data as in panel B but also from TN and TCM CD4+ T cells. #P < .05 vs ART; Wilcoxon rank-sum test. (D) Fold change in the absolute count of CD4+ T cells with different differentiation phenotypes in the peripheral blood at d59 (d13 posttherapy interruption) in the ART and ART+IL-15 groups. Data are depicted as in Figure 2A. #P < .05 vs ART; Wilcoxon rank-sum test. (E) Bar graph and (F) pie charts representing the quality of the SIV-specific (Gag and Env averaged) CD4+ T-cell response at days 46, 59, and 70 in the ART and ART+IL-15 groups. Colors in the pie charts corresponding to different cytokine combinations are indicated at the bottom of panel C. #P < .05 vs d46. (E) Percentage of SIV-specific (Gag and Env averaged) CD4+ T cells with TCM, TTM, or TEM phenotype of total memory cells before treatment interruption (d46) and at days 59 and 70. Data were expressed as in Figure 1B. # = P < .05 vs d46.

Enrico Lugli, et al. Blood. 2011 September 1;118(9):2520-2529.

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