Thesis (M.Sc.) - Cairo University - Faculty of Veterinary Medicine - Department of Virology

HIV infection continues to be a major global health issue and is characterized by a profound dysregulation of various immune cells, including B cells. Recently, increased frequencies of regulatory, granzyme B-expressing B cells have been identified in HIV-infected patients compared to healthy subjects, but their function remains unclear. Due to limitations in studies with HIV-infected individuals, animal studies are needed. To date, the experimental infection of rhesus macaques (Macaca mulatta) with simian immunodefiency virus (SIV) is the best animal model for HIV/AIDS research. The aim of this work was to analyse frequencies, phenotype and the possible function of granzyme B-expressing B cells in healthy and SIV-infected rhesus macaques. Then B cells were purified using magnetic cell separation and different stimulation protocols were applied to induce granzyme B expression in vitro. Finally Co-culture experiments of these in vitro induced granzyme B-expressing B cells with T cells performed. Furthermore, we aimed at analyzing these cells in so-called long-term survivors (LTS), which lack disease progression in the absence of antiretroviral therapy, but can suddenly lose this status and progress to AIDS. By using multicolor flow cytometry the phenotype and frequencies of granzyme B-expressing B cells have been assessed and correlated with other immunologic parameters. Similar to HIV patients, significantly higher frequencies of these cells have been found in the blood of chronically SIV-infected rhesus monkeys compared with uninfected healthy ones

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