933 resultados para Lymphocytes T CD4


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Mmoire numris par la Direction des bibliothques de l'Universit de Montral.

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Mmoire numris par la Direction des bibliothques de l'Universit de Montral.

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Thse numrise par la Direction des bibliothques de l'Universit de Montral.

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Mmoire numris par la Direction des bibliothques de l'Universit de Montral.

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Mmoire numris par la Direction des bibliothques de l'Universit de Montral.

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Mmoire numris par la Direction des bibliothques de l'Universit de Montral.

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Thse numrise par la Direction des bibliothques de l'Universit de Montral.

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Thesis (Master's)--University of Washington, 2016-06

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A decline in the CD4 count is a common feature in HIV/AIDS, suggesting a compromise in immunity of patients. In response, highly active antiretroviral therapy (HAART) is prescribed to slow-down a diminution in the CD4 count and risk of AIDS-related malignancies. However, exercise may improve both the utility and population of innate immune cell components, and may be beneficial for patients with HIV infection. Comparing the effects of different exercises against HAART, on CD4 count, helps in understanding the role and evidence-based application of exercises to ameliorate immune deficiency.

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Feline immunodeficiency virus (FIV) is a naturally occurring lentivirus of domestic cats, which shares many similarities with its human counterpart, human immunodeficiency virus (HIV). FIV infects its main target cell, the CD4+ T lymphocyte, via interactions with its primary receptor CD134 (an activation marker expressed on activated CD4+ T lymphocytes), and, the chemokine receptor CXCR4. According to the different ways in which FIV isolates interact with CD134, FIV may be categorised into two groups. The first group contains strains that tend to dominate during the earlier phase of infection, such as GL8 and CPG41. These strains are characterized by their requirement for an additional interaction with the second cysteine rich domain (CRD2) of the CD134 molecule and are classified as CRD2-dependent strains. The second group, on the other hand, contains either laboratory-adapted isolates or isolates that emerge after several years of infection, such as PPR or the GL8 variants that emerged in cats 6 years post experimental infection and were studied in this thesis. These isolates are designated CRD2-independent as they can infect target cells without interacting with CRD2 of the CD134 molecule. This study provides the first evidence that FIV compartmentalisation is related to FIV-CD134 usage and the tissue availability of CD134+ target cells. In tissue compartments containing high levels of CD134+ cells such as peripheral blood and lymph nodes, CRD2-dependent viruses predominated, whereas CRD2-independent viruses predominated in compartments with fewer CD134+ cells, such as the thymus. The dynamics of CD4+CD134+ T lymphocytes at different stages of FIV infection were also described. The levels of CD4+CD134+ T lymphocytes, which were very high in the early phase, gradually decreased in the later phase of infection. The dynamics of CD4+CD134+ T lymphocyte numbers appeared to correlate with FIV tropism switching, as more CRD2-independent viruses were isolated from cats in the late phase of infection. Moreover, it was observed that pseudotypes bearing Envs of CRD2-dependent variants infected CD134+ target cells more efficiently than pseudotypes bearing Envs of CRD2-independent variants, confirming the selective advantage of CRD2-dependent variants in environments with high levels of CD134+ target cells. In conclusion, this study demonstrated that target cell types and numbers, as well as their dynamics, play important roles in the selection and expansion of FIV variants within the viral quasispecies. Improved understanding of the roles of target cells in FIV transmission and pathogenesis will provide important information required for the development of an improved, more successful protective FIV vaccine and will provide insight into the development of effective vaccines against other lentiviral infections such as HIV.