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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Impaired IFN-γ-secreting capacity in mycobacterial antigen-specific CD4 T cells during chronic HIV-1 infection despite long-term HAART
AIDS, Volume 20, No. 6, Year 2006
Notification
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Description
Objective: To determine whether long-term HAART in chronic HIV-1 infection restores fully functional Mycobacterium tuberculosis (MTB)-specific CD4 T-cell responses. Design: A cross-sectional study of HIV-1-seropositive subjects on continuous HAART for over one year with CD4 cell counts greater than 300 cells/μl and undetectable viraemia, antiretroviral-naive individuals with primary HIV-1 infection (PHI), and healthy bacillus Calmette-Guérin- vaccinated low-risk controls. Methods: Purified protein derivative (PPD)-specific cytokine-secreting CD4 T cells were quantified ex vivo by enzyme-linked immunospot assay and intracellular cytokine staining. Lymphoproliferation was detected by [3H]-thymidine incorporation. Results: PPD-specific IFN-γ-secreting CD4 T cells were markedly reduced in chronic HAART-treated HIV-1-positive and PHI subjects compared with healthy controls [medians 30, 155 and 582 spot-forming cells/million peripheral blood mononuclear cells (PBMC), respectively, P < 0.0001 and P < 0.002], but the frequency of these cells was, nonetheless, significantly greater in viraemic PHI subjects than in aviraemic chronic HIV-1-positive subjects (P < 0.01). In the latter, low frequencies of PPD-specific IL-2 and IL-4-secreting CD4 T cells were also observed. However, lymphoproliferation was evident after the in-vitro stimulation of PBMC with PPD, indicating that MTB-specific T cells were present. The defect in IFN-γ secretion could be overcome by culture with IL-12. Conclusion: Despite an improvement in CD4 T-cell counts after HAART, MTB-specific CD4 T cells from chronically infected patients have impaired IFN-γ-secreting capacity. The early initiation of HAART might preserve functional CD4 T-cell responses to MTB, and warrants evaluation in populations with a high risk of dual infection. © 2006 Lippincott Williams & Wilkins.
Authors & Co-Authors
Sutherland, Rebecca K.
United Kingdom, Oxford
Churchill Hospital
Yang, Hongbing
United Kingdom, Oxford
Churchill Hospital
Scriba, Thomas J.
United Kingdom, Oxford
University of Oxford
Ondondo, Beatrice Omusiro
United Kingdom, Oxford
Churchill Hospital
Robinson, Nicola
United Kingdom, Oxford
University of Oxford
Conlon, Christopher P.
United Kingdom, Oxford
Churchill Hospital
Suttill, Annie
United Kingdom, Oxford
Churchill Hospital
McShane, Helen
United Kingdom, Oxford
Churchill Hospital
Fidler, Sarah J.
United Kingdom, London
Imperial College London School of Medicine
McMichael, Andrew James
United Kingdom, Oxford
Churchill Hospital
Dorrell, Lucy
United Kingdom, Oxford
Churchill Hospital
Statistics
Citations: 63
Authors: 11
Affiliations: 3
Identifiers
Doi:
10.1097/01.aids.0000218545.31716.a4
ISSN:
02699370
Research Areas
Infectious Diseases
Study Design
Cross Sectional Study
Study Approach
Quantitative