The function and regulation of the immune response triggered during malaria is complex and poorly... more The function and regulation of the immune response triggered during malaria is complex and poorly understood, and there is a particular paucity of studies conducted in humans infected with Plasmodium vivax. While it has been proposed that T-cell-effector responses are crucial for protection against blood-stage malaria in mice, the mechanisms behind this in humans remain poorly understood. Experimental models of malaria have shown that the regulatory molecules, cytotoxic T lymphocyte attenuator (CTLA-4), lymphocyte activation gene-3 (LAG-3) and programmed death-1 (PD-1) are involved in the functional impairment of T-cells during infection. The goal of this study was to define the role of these molecules during P. vivax malaria. Here we demonstrate that P. vivax infection triggers the expression of regulatory molecules on T-cells. The pattern of expression differs in CD4(+) and CD8(+) T-cells. Higher frequencies of CD4(+) express more than one regulatory molecule compared to CD8(+) T-...
Cancer immunology, immunotherapy : CII, Jan 18, 2014
The development of cancer immunotherapy has long been a challenge. Here, we report that prophylac... more The development of cancer immunotherapy has long been a challenge. Here, we report that prophylactic vaccination with a highly attenuated Trypanosoma cruzi strain expressing NY-ESO-1 (CL-14-NY-ESO-1) induces both effector memory and effector CD8(+) T lymphocytes that efficiently prevent tumor development. However, the therapeutic effect of such a vaccine is limited. We also demonstrate that blockade of Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) during vaccination enhances the frequency of NY-ESO-1-specific effector CD8(+) T cells producing IFN-γ and promotes lymphocyte migration to the tumor infiltrate. As a result, therapy with CL-14-NY-ESO-1 together with anti-CTLA-4 is highly effective in controlling the development of an established melanoma.
Acta Crystallographica Section F-structural Biology and Crystallization Communications, 2008
Cysteine proteinases from the latex of plants of the family Caricaceae are widely used industrial... more Cysteine proteinases from the latex of plants of the family Caricaceae are widely used industrially as well as in pharmaceutical preparations. In the present work, a 23 kDa cysteine proteinase from Carica candamarcensis latex (designated CMS1MS2) was purified for crystallization using three chromatography steps. The enzyme shows about fourfold higher activity than papain with BAPNA as substrate. Crystals suitable for X-ray diffraction experiments were obtained by the hanging-drop method in the presence of PEG and ammonium sulfate as precipitants. The crystals are monoclinic (space group P2(1)), with unit-cell parameters a = 53.26, b = 75.71, c = 53.23 A, beta = 96.81 degrees , and diffract X-rays to 1.8 A resolution.
The function and regulation of the immune response triggered during malaria is complex and poorly... more The function and regulation of the immune response triggered during malaria is complex and poorly understood, and there is a particular paucity of studies conducted in humans infected with Plasmodium vivax. While it has been proposed that T-cell-effector responses are crucial for protection against blood-stage malaria in mice, the mechanisms behind this in humans remain poorly understood. Experimental models of malaria have shown that the regulatory molecules, cytotoxic T lymphocyte attenuator (CTLA-4), lymphocyte activation gene-3 (LAG-3) and programmed death-1 (PD-1) are involved in the functional impairment of T-cells during infection. The goal of this study was to define the role of these molecules during P. vivax malaria. Here we demonstrate that P. vivax infection triggers the expression of regulatory molecules on T-cells. The pattern of expression differs in CD4(+) and CD8(+) T-cells. Higher frequencies of CD4(+) express more than one regulatory molecule compared to CD8(+) T-...
Cancer immunology, immunotherapy : CII, Jan 18, 2014
The development of cancer immunotherapy has long been a challenge. Here, we report that prophylac... more The development of cancer immunotherapy has long been a challenge. Here, we report that prophylactic vaccination with a highly attenuated Trypanosoma cruzi strain expressing NY-ESO-1 (CL-14-NY-ESO-1) induces both effector memory and effector CD8(+) T lymphocytes that efficiently prevent tumor development. However, the therapeutic effect of such a vaccine is limited. We also demonstrate that blockade of Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) during vaccination enhances the frequency of NY-ESO-1-specific effector CD8(+) T cells producing IFN-γ and promotes lymphocyte migration to the tumor infiltrate. As a result, therapy with CL-14-NY-ESO-1 together with anti-CTLA-4 is highly effective in controlling the development of an established melanoma.
Acta Crystallographica Section F-structural Biology and Crystallization Communications, 2008
Cysteine proteinases from the latex of plants of the family Caricaceae are widely used industrial... more Cysteine proteinases from the latex of plants of the family Caricaceae are widely used industrially as well as in pharmaceutical preparations. In the present work, a 23 kDa cysteine proteinase from Carica candamarcensis latex (designated CMS1MS2) was purified for crystallization using three chromatography steps. The enzyme shows about fourfold higher activity than papain with BAPNA as substrate. Crystals suitable for X-ray diffraction experiments were obtained by the hanging-drop method in the presence of PEG and ammonium sulfate as precipitants. The crystals are monoclinic (space group P2(1)), with unit-cell parameters a = 53.26, b = 75.71, c = 53.23 A, beta = 96.81 degrees , and diffract X-rays to 1.8 A resolution.
Uploads