Human immunity to M. tuberculosis: T cell subsets and antigen processing

Boom, W. Henry; Canaday, David H.; Fulton, Scott A.; Gehring, Adam J.; Rojas, R.M.; Torres, Marta

doi:10.1016/s1472-9792(02)00054-9

Cited by 136 publications

(101 citation statements)

References 72 publications

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“…Current approaches include DNA vaccines, genetically modified viable mycobacteria, and subunit vaccines (12). Traditionally, the search for immunogenic mycobacterial Ags to be included in a subunit vaccine has focused on classical protein Ags stimulating CD4 ϩ T cells (13). More recently, the translation of basic research into vaccine design prompted the search for unconventional Ags that stimulate ␥␦ T cells or CD1-restricted T cells (14 -16).…”

mentioning

confidence: 99%

Mycobacterial Lipopeptides Elicit CD4+ CTLs in Mycobacterium tuberculosis-Infected Humans

Bastian¹,

Braun

Bruns³

et al. 2008

The Journal of Immunology

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In searching for immunogenic molecules with the potential to induce protective immune responses against tuberculosis, we developed an ex vivo model to study frequency, phenotype, and effector functions of human T lymphocytes recognizing hydrophobic Ags of Mycobacterium tuberculosis (M.Tb). To obtain unbiased results, we characterized T lymphocytes responding to a crude cell wall extract (chloroform methanol extract of M.Tb (M.Tb-CME)) containing a broad spectrum of mycobacterial glycolipids and lipopeptides. A significant proportion of T lymphocytes recognized M.Tb-CME (290 IFN-γ+ T cells/105 PBMCs) and developed to effector memory cells as determined by the expression of CD45RO and the chemokine receptors CXCR3 and CCR5. Expanded lymphocytes fulfilled all criteria required for an efficient immune response against tuberculosis: 1) release of macrophage-activating Th1 cytokines and chemokines required for the spatial organization of local immune responses, 2) cytolytic activity against Ag-pulsed macrophages, and 3) recognition of infected macrophages and killing of the intracellular bacteria. Phenotypically, M.Tb-CME-expanded cells were CD4+ and MHC class II restricted, challenging current concepts that cytotoxic and antimicrobial effector cells are restricted to the CD8+ T cell subset. Pretreatment of M.Tb-CME with protease or chemical delipidation abrogated the biological activity, suggesting that responses were directed toward mycobacterial lipopeptides. These findings suggest that lipidated peptides are presented by M.Tb-infected macrophages and elicit CD4+ cytolytic and antimicrobial T lymphocytes. Our data support an emerging concept to include hydrophobic microbial Ags in vaccines against tuberculosis.

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mentioning

confidence: 99%

Mycobacterial Lipopeptides Elicit CD4+ CTLs in Mycobacterium tuberculosis-Infected Humans

Bastian¹,

Braun

Bruns³

et al. 2008

The Journal of Immunology

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“…13,14 MTB is able to hijack the intracellular mechanisms of pathogen killing in macrophages creating an ideal environment for replication and growth. 15 Memory cells will be present until the death of the infected subject. The T cells' repertoire will form the main response leading to granuloma formation and infection containment, influencing susceptibility to or protection from the disease.…”

Section: Discussionmentioning

confidence: 99%

Tuberculous Meningoencephalitis in a Patient with Hairy Cell Leukemia in Complete Remission

Girardi¹,

Paviglianiti²,

Cirillo³

et al. 2012

J Clin Exp Hematopathol

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“…Once infected, these macrophages release a host of cytokines that recruit several immunologically active cells such as the T-cells which release interferon-g (IFNg) which in combination with tumor necrosis factor-a (TNFa) activate macrophages to eliminate the pathogen. 61 Marcin Wlodarczyk (University of Lodz, Poland) is interested in the profile of mycobacterial antigen driven cytokine responses and the expression of signal transduction receptors in TB. Two hundred and eighteen BCG vaccinated, HIV-/TBC patients were chosen for the study.…”

Section: Host Responses To M Tuberculosismentioning

confidence: 99%

Early diagnosis and effective treatment regimens are the keys to tackle antimicrobial resistance in tuberculosis (TB): A report from Euroscicon's international TB Summit 2016

et al. 2016

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To say that tuberculosis (TB) has regained a strong foothold in the global human health and wellbeing scenario would be an understatement. Ranking alongside HIV/AIDS as the top reason for mortality due to a single infectious disease, the impact of TB extends far into socio-economic context worldwide. As global efforts led by experts and political bodies converge to mitigate the predicted outcome of growing antimicrobial resistance, the academic community of students, practitioners and researchers have mobilised to develop integrated, inter-disciplinary programmes to bring the plans of the former to fruition. Enabling this crucial requirement for unimpeded dissemination of scientific discovery was the TB Summit 2016, held in London, United Kingdom. This report critically discusses the recent breakthroughs made in diagnostics and treatment while bringing to light the major hurdles in the control of the disease as discussed in the course of the 3-day international event. Conferences and symposia such as these are the breeding grounds for successful local and global collaborations and therefore must be supported to expand the understanding and outreach of basic science research.

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Human immunity to M. tuberculosis: T cell subsets and antigen processing

Cited by 136 publications

References 72 publications

Mycobacterial Lipopeptides Elicit CD4+ CTLs in Mycobacterium tuberculosis-Infected Humans

Mycobacterial Lipopeptides Elicit CD4+ CTLs in Mycobacterium tuberculosis-Infected Humans

Tuberculous Meningoencephalitis in a Patient with Hairy Cell Leukemia in Complete Remission

Early diagnosis and effective treatment regimens are the keys to tackle antimicrobial resistance in tuberculosis (TB): A report from Euroscicon's international TB Summit 2016

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