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: 5.78). 01/2009; 198(11):1590-8. DOI: 10.1086/593017
Source: PubMed

ABSTRACT 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, Aug 23, 2015
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    • "Apart from the effects on HIV replication, M. tuberculosis infection has also been shown to down-regulate the proinflammatory and antigen-presenting abilities, and activate the anti-inflammatory functions of DCs (Talaat et al., 2006). DC-mediated activation of T cells is reportedly impaired in HIV infection, and migration of DCs along with HIV contributes to efficient viral dissemination (Wang et al., 2009; Geldmacher et al., 2008; Geijtenbeek et al., 2000). Wax-D has also been implicated in the activation of HIV replication by enhancing TNF-a and IL-6 production by DCs (Briken et al., 2004), which could give rise to increased HIV-1 replication furthering immunosuppression. "
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    • "Thus, mucosal CD4 memory T-cell depletion may provide a potential mechanism to account for disrupted T-cell function in early HIV infection, although whether similar events occur in the lung mucosa has not yet been established [Brenchley et al., 2008]. Indeed, primary HIV infection is associated with decreased PPD-specific IFN-secreting T cells [Sutherland et al., 2006; Geldmacher et al., 2008] and ESAT (early secreted antigenic target)-6–specific T cells [Geldmacher et al., 2008] in the blood, suggesting that early depletion of memory T cells may affect specific immunity to TB. Lung lavage enzymelinked immunospot (ELISPOT) studies also suggest decreased bacillus Calmette-Gue´rin (BCG)– or PPD-specific pulmonary CD4 T cells in asymptomatic HIV-infected persons compared with HIV-negative persons [Kalsdorf et al., 2009]. HIV–TB coinfection may also be associated with increased serum levels of IL-4, an anti-Th1 type cytokine that hinders immune response to MTb [Dheda et al., 2005]. "
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    • "During clinically latent TB, the majority of MTB-specific CD4 T cells expressed CD27 and can be considered as having a central memory-like phenotype (CCR7 was not measured); however, they also expressed higher levels of CCR5 compared with the total memory compartment (Geldmacher et al., 2008). In contrast, CMV-specific CD4 T cells had a highly differentiated effector memory-like phenotype. "
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