Initiation of the adaptive immune response to Mycobacterium tuberculosis depends on antigen production in the local lymph node, not the lungs
Open accessAbstract
The onset of the adaptive immune response to Mycobacterium tuberculosis is delayed compared with that of other infections or immunization, and allows the bacterial population in the lungs to expand markedly during the preimmune phase of infection. We used adoptive transfer of M. tuberculosis Ag85B-specific CD4+ T cells to determine that the delayed adaptive response is caused by a delay in initial activation of CD4+ T cells, which occurs earliest in the local lung-draining mediastinal lymph node. We also found that initial activation of Ag85B-specific T cells depends on production of antigen by bacteria in the lymph node, despite the presence of 100-fold more bacteria in the lungs. Although dendritic cells have been found to transport M. tuberculosis from the lungs to the local lymph node, airway administration of LPS did not accelerate transport of bacteria to the lymph node and did not accelerate activation of Ag85B-specific T cells. These results indicate that delayed initial activation of CD4+ T cells in tuberculosis is caused by the presence of the bacteria in a compartment that cannot be mobilized from the lungs to the lymph node, where initial T cell activation occurs.
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Memory T cells require an extended period of infection, 7-10 days, before controlling pathogen replication in murine tuberculosis and SIV macaque studies.
“Studies of the ability of memory T cells to control viral and bacterial growth suggest that both CD4+ T cells (in murine tuberculosis42) and CD8+ T cells (in simian immunodeficiency virus infection of macaques43,44) require an extended period of infection (7–10 days) before they are mobilized to control pathogen replication.”
From Prospects for durable immune control of SARS-CoV-2 and prevention of reinfection (2021) · cites this paper as [42]
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- Authors
- Wolf, A. J., Desvignes, L., Linas, B., Banaiee, N., Tamura, T., Takatsu, K., & Ernst, J. D.
- Affiliations
- University of California, San Francisco (US)
- 1Division of Infectious Diseases, Department of Medicine
- National Institute of Infectious Diseases (JP)
- Institute of Medical Science, The University of Tokyo (JP)
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2007-12-24
- Volume
- 205
- Issue
- 1
- Pages
- 105-115
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2234384
- OpenAlex
- W2100872199
- Cited by
- 580
- References
- 40
- Citations by year
- 2026: 23 · 2025: 29 · 2024: 25 · 2023: 26 · 2022: 26 · 2021: 28 · 2020: 27 · 2019: 35 · 2018: 27 · 2017: 27 · 2016: 28 · 2015: 37 · 2014: 51 · 2013: 33 · 2012: 39
- FWCI
- 18.69
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-sa)
- Funders
- National Institute of Allergy and Infectious Diseases (L30 AI061958, R01AI051242, K08AI061105)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- Mycobacterium tuberculosis, adaptive immune response, CD4+ T cell activation, Ag85B, mediastinal lymph nodes, lung-draining lymph nodes, dendritic cells, bacterial transport, lipopolysaccharide, adoptive transfer
- MeSH terms
- Acyltransferases, Animals, Antigens, Bacterial, Bacterial Proteins, Dendritic Cells, Immune System, Lung, Lymph Nodes, Lymphocyte Activation, Macrophages, Mice, Inbred C57BL, Models, Biological, Mycobacterium tuberculosis, T-Lymphocytes, Time Factors, CD4-Positive T-Lymphocytes, Polymerase Chain Reaction, Cell Proliferation, Mice
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