Thesis (M.Med.(Haematology)), Faculty of Health Sciences, University of the Witwatersrand, 2009 / 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.
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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.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/7484 |
| Date | 28 January 2010 |
| Creators | Mayne, Elizabeth Sarah |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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