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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Available from: Michael Hoelscher, Oct 08, 2015
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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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    ABSTRACT: With 1.4 million deaths and 8.7 million new cases in 2011, tuberculosis (TB) remains a global health care problem and together with HIV and Malaria represents the one of the three infectious diseases world-wild. Control of the global TB epidemic has been impaired by the lack of an effective vaccine, by the emergence of drug-resistant forms of Mycobacterium tuberculosis (Mtb) and by the lack of sensitive and rapid diagnostics. It is estimated, by epidemiological reports, that one third of the world’s population is latently infected with Mtb, but the majority of infected individuals develops long-lived protective immunity, which controls and contains Mtb in a T cell-dependent manner. Development of TB disease results from interactions among the environment, the host, and the pathogen, and known risk factors include HIV coinfection, immunodeficiency, diabetes mellitus, overcrowding, malnutrition, and general poverty; therefore an effective T cell response determines whether the infection resolves or develops into clinically evident disease. Consequently, there is great interest in determining which T cells subsets mediate anti-mycobacterial immunity, delineating their effector functions. On the other hand, many aspects remain unsolved in understanding why some individuals are protected from Mtb infection while others go on to develop disease.Several studies have demonstrated that CD4+ T cells are involved in protection against Mtb, as supported by the evidence that CD4+ T cell depletion is responsible for Mtb reactivation in HIV-infected individuals. There are many subsets of CD4+ T cells, such as T-helper 1 (Th1), Th2, Th17, and regulatory T cells (Tregs), and all these subsets cooperate or interfere with each other to control infection; the dominant subset may differ between active and latent Mtb infection cases. Mtb-specific CD4+ Th1 cell response is considered to have a protective role for the ability to produce cytokines such as IFN- or TNF- that contribute to
    Frontiers in Immunology 04/2014; 5:180. DOI:10.3389/fimmu.2014.00180
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    • "Overall, however, survival to M. tuberculosis relies on the presence of CD4+ T cells which play a fundamental role in inhibiting its replication and protect from active disease. Indeed CD4 lymphopenic patients with or without HIV infection are at increased risk of developing active TB.52 Although CD4+ T lymphocytes have been considered to be the primary source of IFN-γ and to be protective through its secretion, this is not the case. "
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    Mediterranean Journal of Hematology and Infectious Diseases 01/2014; 6(1):e2014027. DOI:10.4084/MJHID.2014.027
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    • "Distinct HIV replication in Th1Th17 vs. Th1 cells is consistent with findings by other groups that CMV-specific but not M. tuberculosis-specific cells are protected from HIV infection by an autocrine production of CCR5 binding chemokines [32,33]. Differences in HIV permissiveness between Th1Th17 and Th1 cells may account for the depletion of M. tuberculosis-specific cells [34] and the deleterious consequences of CMV-specific cell persistence in HIV-infected subjects [35]. Although Th1Th17 and Th1 cells produce similar CCL3 and CCL5 levels, a superior CCR5 expression on Th1Th17 cells ex vivo argue in favor of their increased ability to support R5 HIV entry [31]. "
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