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Title: Antigen-presenting cell function in HIV infection and tuberculosis
Author: Dorrell, Lucy
ISNI:       0000 0001 3429 5167
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 1997
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The aim of this project was to investigate the effect of HIV infection on the function of antigen-presenting cells (APCs) in the lung. Processing and presentation of mycobacterial antigens were chosen as parameters of APC function as tuberculosis is a frequent and important complication of HIV infection. A model system was developed using the responses of mycobacterial antigen-specific T cell clones, isolated from a healthy control subject, to assess the integrity of antigen processing and presentation by peripheral blood mononuclear cells (PBMCs) from HIV-seropositive patients at all stages of disease. The system was then applied to broncho-alveolar lavage (BAL) cells. Collaborative studies using T cell clones specific to an HIV-1MN gp120V3 loop peptide, derived from an HIV-seronegative control, revealed a correlation between the responsiveness of these T cell clones to peptide presented by PBMCs from HIV-seropositive individuals and susceptibility of the T cell clones to inhibition by a monoclonal antibody to CD4 (anti-CD4 mAb). The mycobacterial antigen-specific T cell clones did not respond to peptide, mycobacterial extract or recombinant 19 kD antigens when these were presented by PBMCs from HIV-infected individuals but responded normally when PBMCs from healthy controls were used; they were found to be readily inhibited by anti-CD4 mAb, thus confirming the initial observations with the V3 loop-specific T cells (designated 'CD4-dependent'). The study was extended to include responses to influenza antigens: a haemagglutinin-specific T cell clone of intermediate CD4-dependency responded to peptide presented by PBMCs from HIV-infected individuals were either defective as APCs or were inhibitory to T cells in some other way.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Medicine