Early Depletion of Mycobacterium tuberculosis –Specific T Helper 1 Cell Responses after HIV‐1 Infection

Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
The Journal of Infectious Diseases (Impact Factor: 6). 01/2009; 198(11):1590-8. DOI: 10.1086/593017
Source: PubMed


The acid-fast bacillus Mycobacterium tuberculosis is often the first manifestation of acquired immunodeficiency syndrome in patients infected with human immunodeficiency virus (HIV). This study was conducted to better understand the mechanism underlying M. tuberculosis-specific pathogenicity early after onset of HIV infection.
M. tuberculosis-specific T helper 1 (Th1) cells were studied in HIV negative (n=114) and chronically HIV infected (n=68) Tanzanian subjects by using early secreted antigenic target 6 (ESAT6) protein or tuberculin (purified protein derivative) with interferon-gamma ELISPOT and intracellular cytokine staining. In a longitudinal study, the effect of acute HIV infection on M. tuberculosis-specific Th1 cells was determined by polychromatic flow cytometric analysis in 5 subjects with latent M. tuberculosis infection who became infected with HIV.
In tuberculosis (TB)-asymptomatic subjects (i.e., subjects with unknown TB status who did not show clinical signs suggestive of TB), chronic HIV infection was associated with a decreased percentage of subjects with detectable M. tuberculosis-specific Th1 cells (P< .001) a decrease which was not observed among subjects with active TB. Acute HIV infection induced a rapid depletion of M. tuberculosis-specific Th1 cells in 4 subjects remained TB asymptomatic, whereas the population of these cells remained stable in subjects who remained HIV negative (P< .01).
Taken together, these data suggest a mechanism of rapid M. tuberculosis-specific Th1 cell depletion that may contribute to the early onset of TB in individuals with latent M. tuberculosis infection who become HIV infected.

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    • "Studies of human disease have characterized functional defects in CD4 T cells in TB-HIV co-infection by the analysis of cytokine production (e.g., IFN-γ) by CD4 cells in response to Mtb Ags (139–142) and by the analysis of phenotype distribution of CD4 T cells in lymphoid tissue, peripheral blood, and at the sites of disease (139, 143, 144). The correlation of different phenotypes of Ag-specific-CD4 T cells, and their role on the protection or susceptibility to infection, has been clearly demonstrated by the emerging characterization of polyfunctional CD4 T cells in TB-HIV co-infection. "
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