Browsing by Author "Ahimbisibwe, Gift"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Feasibility and Acceptability of Undertaking Postmortem Studies for Tuberculosis Medical Research in a Low Income Country
    (Frontiers in immunology, 2023-12-06) Ahimbisibwe, Gift; Nakibuule, Marjorie; Mulwana, Rose; Kyazze, Andrew; Cose, Stephen
    If we are to break new ground in difficult-to-treat or difficult-to-vaccinate diseases (such as HIV, malaria, or tuberculosis), we must have a better understanding of the immune system at the site of infection in humans. For tuberculosis (TB), the initial site of infection is the lungs, but obtaining lung tissues from subjects suffering from TB has been limited to bronchoalveolar lavage (BAL) or sputum sampling, or surgical resection of diseased lung tissue. We examined the feasibility of undertaking a postmortem study for human tuberculosis research at Mulago National Referral Hospital in Kampala, Uganda. Postmortem studies give us an opportunity to compare TB-involved and -uninvolved sites, for both diseased and non-diseased individuals. We report good acceptability of the next-of-kin to consent for their relative’s tissue to be used for medical research; that postmortem and tissue processing can be undertaken within 8 hours following death; and that immune cells remain viable and functional up to 14 hours after death. Postmortem procedures remain a valuable and essential tool both to establish cause of death, and to advance our medical and scientific understanding of infectious diseases.
  • Thumbnail Image
    Item
    Tissue-specific T cell profiles in Mycobacterium tuberculosis uninfected IGRA negative and positive individuals
    (Frontiers in Tuberculosis, 2025-03-06) Ahimbisibwe, Gift; Nakibuule, Marjorie; Bisoboka, Claire Precious; Biraro, Irene Andia; Cose, Stephen
    Interferon-gamma release assays (IGRAs), such as the T-SPOT.TB and QuantiFERON-TB Gold, are commonly used to detect immune responses to Mycobacterium tuberculosis (M.tb) and identify latent TB infection. However, their role in reflecting immune dynamics within tissues, especially in the absence of active disease, remains unclear. Post-mortem tissues, including lung, lymph nodes, spleen, and bronchoalveolar lavage, were collected from apparently healthy, HIV-negative road traffic accident victims. M.tb infection was ruled out using liquid MGIT culture, while M.tb exposure history was assessed with the TSPOT.TB assay. T and B cell phenotyping was performed using a 29-color flow cytometry panel, with data analyzed in FlowJo and GraphPad Prism. Of the 52 individuals recruited, 48% were IGRA-positive (TSPOT+). Using a 29-color flow cytometry panel, we analyzed T and B cell populations across various tissues. We observed similar overall frequencies of CD3, CD4, CD8, and CD19 cells, as well as memory T and B cell subsets defined by CCR7/CD45RA and IgD/CD27 between TSPOT+ and TSPOT individuals. Notably, in the lungs, TSPOT+ individuals exhibited a higher frequency of CD4+ tissue-resident memory (TRM) T cells, along with increased expression of KLRG1, a marker of terminal differentiation, on mature CD4+CD27 T cells. This phenotype was specific to CD4 T cells in the lungs, highlighting the known role of CD4 T cells in TB immunity and their localization to the primary site of infection. Our findings suggest that IGRA positivity, while indicating immune memory, may also be associated with highly differentiated CD4 T cells in tissue-specific compartments, particularly in the lungs. These localized immune changes raise important questions about the long-term effects of chronic immune engagement following repeated M.tb exposure in endemic settings. Further research is needed to assess the clinical implications of these findings, including their impact on susceptibility to future infections or disease progression.