Cited by 547Tuberculosis Research and EpidemiologyImmunotherapy and Immune ResponsesImmune responses and vaccinations

Apoptosis facilitates antigen presentation to T lymphocytes through MHC-I and CD1 in tuberculosis

Schaible, Ulrich E, Winau, Florian, Sieling, Peter A, Fischer, Karsten, Collins, Helen L, Hagens, Kristine, Modlin, Robert L, Brinkmann, Volker +1 more·2003·Nature Medicine

Abstract

Protective immunity against Mycobacterium tuberculosis involves major histocompatibility complex class I (MHC-I)- and CD1-restricted CD8 T cells, but the mechanisms underlying antigen delivery to antigen-presenting molecules remain enigmatic. Macrophages, the primary host cells for mycobacteria, are CD1-negative. Here we show that M. tuberculosis phagosomes are secluded from the cytosolic MHC-I processing pathway and that mycobacteria-infected cells lose their antigen-presenting capacity. We also show that mycobacteria induce apoptosis in macrophages, causing the release of apoptotic vesicles that carry mycobacterial antigens to uninfected antigen-presenting cells (APCs). Inhibition of apoptosis reduced transfer of antigens to bystander cells and activation of CD8 T cells. Uninfected dendritic cells, which engulfed extracellular vesicles, were indispensable for subsequent cross-presentation of antigens, through MHC-I and CD1b, to T cells from mycobacteria-sensitized donors. This new 'detour' pathway for presentation of antigens from a phagosome-contained pathogen shows the functional significance of infection-induced apoptosis in the activation of CD8 T cells specific for both protein and glycolipid antigens in tuberculosis.

Integrity signals

Registry

Crossref · 10.1038/nm906

Cites

41 of 41 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Apoptotic blebs from infected macrophages can promote cross presentation and protective T-cell immunity.

    “As reported previously, apoptotic blebs from infected MΦs can also promote cross presentation and protective T-cell immunity (137, 157).”

    From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [157]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Schaible, U. E., Winau, F., Sieling, P. A., Fischer, K., Collins, H. L., Hagens, K., Modlin, R. L., Brinkmann, V., & Kaufmann, S. H. E.
Affiliations
  • Max Planck Society (DE)
  • University of California, Los Angeles (US)
Corresponding author
Schaible, Ulrich E
Venue
Nature Medicine
Published
2003-07-20
Volume
9
Issue
8
Pages
1039-1046
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
OpenAlex
W2008626549
Cited by
546
References
41
Citations by year
2026: 8 · 2025: 19 · 2024: 10 · 2023: 11 · 2022: 22 · 2021: 15 · 2020: 8 · 2019: 12 · 2018: 16 · 2017: 28 · 2016: 24 · 2015: 22 · 2014: 39 · 2013: 23 · 2012: 28
FWCI
22.87
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • Research Portal (King's College London) (submittedVersion)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (submittedVersion)
Funders
  • Deutsche Forschungsgemeinschaft (SFB421)
  • Bundesministerium für Bildung und Forschung
Topics
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords
tuberculosis, Mycobacterium tuberculosis, apoptosis, antigen presentation, MHC class I, CD1b, CD8+ T cells, cross-presentation, dendritic cells, macrophages, phagosome, extracellular vesicles, glycolipid antigens, protective immunity
MeSH terms
Animals, Antigen-Presenting Cells, Antigens, Bacterial, Genes, MHC Class I, Humans, Listeria monocytogenes, Lymphocyte Activation, Macrophages, Mycobacterium tuberculosis, Phagosomes, Tuberculosis, Histocompatibility Antigens Class I, Apoptosis, Antigen Presentation, CD8-Positive T-Lymphocytes, Antigens, CD1, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review