Figure 5
Prevention of mucosal transmission of HIV-1 in hu-BLT mice transduced with b12-IgA. Humanized-BLT mice were challenged with R5 tropic HIV-1 (JR-CSF) through intravaginal route at 14 to 20 weeks after transplantation or left unchallenged (no virus). Peripheral blood of the mice was collected periodically. Mice were killed after 8 to 10 weeks of HIV-1 challenge and lymphocytes from various tissues were isolated and analyzed by flow cytometry. (A) Protection of mucosal CD4+ T cells in hu-BLT-b12a mice from HIV-1 infection. Flow cytometry of mucosal lymphocytes isolated from intestinal intraepithelium (gut IEL), intestinal lamina propria (gut LPL) and female genital tract (genital) of hu-BLT mice that are transduced with b12-IgA gene (BLT-b12a) or with control gene (BLT-Ctrl). (B) Proportion of CD4+ T cells of primary (BM indicates bone marrow) or secondary (SPL indicates spleen) lymphoid organs and periphery. Cells were pregated on CD45+CD3+ cells (A-B). (C) Percent CD4+ T cells in CD45+CD3+ human T cells in the tissues of hu-BLT mice after HIV-1 infection. Data are mean ± SEM (n = 3-5, *P ≤ .05, **P ≤ .01). (D) Changes of CD4/CD8 ratio in PBMCs of hu-BLT mice after HIV-1 mucosal challenge. Data are mean ± SEM at each time points (weeks after challenge) open circle: no challenge; purple circle: HIV-1 challenge in control gene-transduced hu-BLT mice; green circle: HIV-1 challenge in b12-IgA-transduced hu-BLT mice. Unpaired t test showed the b12-IgA transduced group had significantly higher CD4:CD8 ratios than the control vector transduced group after HIV challenge. (n = 3-6, P < .05, P = .0148) All data points in each group regardless of time were included in the t test. (E) Differential expression of CCR5, the HIV-1 coreceptor level in human CD4+ T cells in hu-BLT mice. Histograms show the proportion of CCR5+CD4+ T cells in PBMC, gut lymphocyte, genital tract lymphocytes of hu-BLT mouse model. (F) Immunohistochemical staining of HIV-1 p24 protein in indicated tissues of hu-BLT mice after HIV-1 mucosal challenge. (SPL: spleen, SI: small intestine) Samples were examined on an Olympus BX-51 microscope (40× objective lens) and photographed using a Spot Digital Camera. (G) P24+ cells were determined by counting immunohistochemically stained cells from genital and intestinal tract tissue sections of hu-BLT mice. (n = 3-5, mean ± SEM).

Prevention of mucosal transmission of HIV-1 in hu-BLT mice transduced with b12-IgA. Humanized-BLT mice were challenged with R5 tropic HIV-1 (JR-CSF) through intravaginal route at 14 to 20 weeks after transplantation or left unchallenged (no virus). Peripheral blood of the mice was collected periodically. Mice were killed after 8 to 10 weeks of HIV-1 challenge and lymphocytes from various tissues were isolated and analyzed by flow cytometry. (A) Protection of mucosal CD4+ T cells in hu-BLT-b12a mice from HIV-1 infection. Flow cytometry of mucosal lymphocytes isolated from intestinal intraepithelium (gut IEL), intestinal lamina propria (gut LPL) and female genital tract (genital) of hu-BLT mice that are transduced with b12-IgA gene (BLT-b12a) or with control gene (BLT-Ctrl). (B) Proportion of CD4+ T cells of primary (BM indicates bone marrow) or secondary (SPL indicates spleen) lymphoid organs and periphery. Cells were pregated on CD45+CD3+ cells (A-B). (C) Percent CD4+ T cells in CD45+CD3+ human T cells in the tissues of hu-BLT mice after HIV-1 infection. Data are mean ± SEM (n = 3-5, *P ≤ .05, **P ≤ .01). (D) Changes of CD4/CD8 ratio in PBMCs of hu-BLT mice after HIV-1 mucosal challenge. Data are mean ± SEM at each time points (weeks after challenge) open circle: no challenge; purple circle: HIV-1 challenge in control gene-transduced hu-BLT mice; green circle: HIV-1 challenge in b12-IgA-transduced hu-BLT mice. Unpaired t test showed the b12-IgA transduced group had significantly higher CD4:CD8 ratios than the control vector transduced group after HIV challenge. (n = 3-6, P < .05, P = .0148) All data points in each group regardless of time were included in the t test. (E) Differential expression of CCR5, the HIV-1 coreceptor level in human CD4+ T cells in hu-BLT mice. Histograms show the proportion of CCR5+CD4+ T cells in PBMC, gut lymphocyte, genital tract lymphocytes of hu-BLT mouse model. (F) Immunohistochemical staining of HIV-1 p24 protein in indicated tissues of hu-BLT mice after HIV-1 mucosal challenge. (SPL: spleen, SI: small intestine) Samples were examined on an Olympus BX-51 microscope (40× objective lens) and photographed using a Spot Digital Camera. (G) P24+ cells were determined by counting immunohistochemically stained cells from genital and intestinal tract tissue sections of hu-BLT mice. (n = 3-5, mean ± SEM).

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