Progressive differentiation and selection of the fittest in the immune response
Abstract
T cells are stimulated by stochastic exposure to antigen-presenting cells and cytokines. We review evidence that the level of signal that is accumulated determines progression through hierarchical thresholds for proliferation and differentiation, leading to the generation of various intermediates and effector T cells. These cells are then selected to enter the memory pool according to their fitness--that is, their capacity to access and use survival signals. We suggest that the intermediates that are generated by antigenic stimulation of T and B cells persist as central memory cells, which can mount secondary responses to antigen and maintain appropriate levels of effector cells and antibodies throughout the lifetime of an individual.
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The capacity to continuously generate effector memory T cells replenishes the effector memory T cell pool and helps maintain a constant memory T cell repertoire for a human lifetime, despite finite effector cell lifespan and reduced thymus function.
“The capacity to continuously generate effector memory T cells will replenish the effector memory T cell pool, and help maintain a constant repertoire of memory T cells for a human lifetime, despite the finite lifespan of individual effector cells and reduced thymus function [68].”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [68]
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- Authors
- Lanzavecchia, A., & Sallusto, F.
- Affiliations
- Institute for Research in Biomedicine (CH)
- Corresponding author
- Lanzavecchia, Antonio
- Sallusto, Federica
- Venue
- Nature Reviews Immunology
- Published
- 2002-12
- Volume
- 2
- Issue
- 12
- Pages
- 982-987
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- OpenAlex
- W2886274086
- Cited by
- 495
- References
- 69
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 6 · 2023: 10 · 2022: 13 · 2021: 15 · 2020: 7 · 2019: 8 · 2018: 13 · 2017: 12 · 2016: 13 · 2015: 19 · 2014: 13 · 2013: 18 · 2012: 15
- FWCI
- 3.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institute for Research in Biomedicine
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Helmut Horten Stiftung
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- T cell differentiation, T cell selection, signal threshold, antigen-presenting cells, cytokines, T cell proliferation, central memory T cells, effector T cells, B cells, memory B cells, survival signaling, secondary immune response
- MeSH terms
- Animals, Antigens, B-Lymphocytes, Cell Division, Hematopoietic Stem Cells, Humans, Immunity, Active, Immunologic Memory, T-Lymphocytes, Lymphopoiesis
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