Theses and Dissertations (Pathology)

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    The role of regulatory T cells in adults in South Africa with active tuberculosis
    (2010-01-28T10:11:24Z) Mayne, Elizabeth Sarah
    Introduction Regulatory T cells (Tregs) are increasingly being recognized as key immunological players in immunosuppression and have been seen to be permissive for certain infections. Aim This study aimed to elucidate the role that Tregs play in symptomatic infection with Mycobacterium tuberculosis (TB), both with and without co-infection with human immunodeficiency virus type 1 (HIV 1) by quantification of these cells at ex vivo. It was then attempted to characterise the behaviour of FoxP3 positive cells in culture with stimulation. Methods Peripheral blood mononuclear cells were purified from uninfected controls, patients with active TB, patients with HIV infection and patients with HIV infection and active TB. The frequencies of Tregs were assessed by flow cytometry at ex vivo and again after four days of culture with stimulation with anti-CD3, Purified protein derivative, tetanus toxoid and HIV peptide superpools (gag and nef). These frequencies were compared between the four groups of patients. The ability of Tregs and effector T cells to proliferate was also assessed. Interferon-γ secretion was used as a measure of effector T cell response to stimulation. vi Results Frequencies of Tregs were significantly reduced in patients with active TB as compared with HIV infected patients and uninfected controls. Co-infected individuals showed a broad range of frequencies which were not significantly different from controls. These frequencies remained stable in culture with the exception of those individuals infected with HIV who showed a decline in the frequency of those cells expressing FoxP3 over the period. Cells expressing FoxP3 were not anergic and responded to stimulation. HIV specific proteins, in addition, resulted in specific effects on the Tregs with a positive interferon response to gag correlating with increased Treg frequencies and FoxP3 expression in CD4+ T cells correlated with the proliferative response of CD4+ T cells to Nef in HIV infected individuals. Conclusions This study shows significant differences of frequencies of FoxP3 positive producing cells in the peripheral blood at ex vivo in patients with active TB. The function of these cells in this population is uncertain and further functional data and long-term clinical follow-up is required. In addition, the frequencies of these cells remained constant over time and showed proliferative response to stimuli (most notably CD3) suggesting that these cells may be generated in the periphery.