Immunosuppression during active tuberculosis is characterized by decreased interferon-γ production and CD25 expression with elevated forkhead box P3, transforming growth factor-β, and interleukin-4 mRNA levels

Date
2007
Authors
Roberts T.
Beyers N.
Aguirre A.
Walzl G.
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Journal ISSN
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Abstract
The balance between effector and regulatory responses after Mycobacterium tuberculosis infection may dictate outcome and progression to active disease. We investigated effector and regulatory T cell responses in bacille Calmette-Guérin (BCG)-stimulated peripheral blood mononuclear cells and whole blood cultures from persons with active tuberculosis (TB), persons with TB at the end of 6 months of treatment, and healthy control subjects with latent TB infection. All 3 groups displayed BCG-induced increases in effector and regulatory T cell phenotypes as defined by CD4+CD25lo and CD4+CD25hi T cells, respectively. In case patients with active disease, BCG stimulation induced the lowest increase of CD25, CD4 +CD25hi, CTLA-4, and interferon-γ. However, these case patients expressed the highest mRNA levels of forkhead box P3, transforming growth factor (TGF)-β, and interleukin (IL)-4 and a lower T-bet:GATA-3 ratio. There were no significant differences in IL-4δ2, IL-10, or TGF-β receptor-II mRNA expression between groups. Together, these results suggest that immunosuppression seen after mycobacterial stimulation in case patients with active TB is associated with naturally occurring regulatory T cells. © 2007 by the Infectious Diseases Society of America. All rights reserved.
Description
Keywords
BCG vaccine, ethambutol, gamma interferon, interleukin 10, interleukin 2 receptor alpha, interleukin 4, isoniazid, messenger RNA, pyrazinamide, rifampicin, transcription factor FOXP3, transcription factor GATA 3, transcription factor T bet, transforming growth factor beta, transforming growth factor beta receptor 2, antigen expression, article, CD4+ CD25+ T lymphocyte, cellular immunity, controlled study, effector cell, human, human cell, immune deficiency, interferon production, lung tuberculosis, mononuclear cell, Mycobacterium tuberculosis, nonhuman, phenotype, priority journal, regulatory T lymphocyte, Antigens, CD, Antigens, CD3, BCG Vaccine, CD4 Lymphocyte Count, DNA Primers, Forkhead Transcription Factors, Gene Expression Regulation, Humans, Immunosuppression, Interferon Type II, Interleukin-2 Receptor alpha Subunit, Interleukin-4, Lymphocyte Count, Mycobacterium tuberculosis, Polymerase Chain Reaction, RNA, Messenger, T-Lymphocytes, Transforming Growth Factor beta, Tuberculosis
Citation
Journal of Infectious Diseases
195
6