Cited by 1,635T-cell and B-cell ImmunologyImmunotherapy and Immune ResponsesImmune responses and vaccinations

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CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes

Janssen, Edith M., Lemmens, Edward E., Wolfe, Tom, Christen, Urs, von Herrath, Matthias G., Schoenberger, Stephen P.·2003·Nature

DOI 10.1038/nature01441

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Abstract

A long-standing paradox in cellular immunology concerns the conditional requirement for CD4+ T-helper (T(H)) cells in the priming of cytotoxic CD8+ T lymphocyte (CTL) responses in vivo. Whereas CTL responses against certain viruses can be primed in the absence of CD4+ T cells, others, such as those mediated through 'cross-priming' by host antigen-presenting cells, are dependent on T(H) cells. A clearer understanding of the contribution of T(H) cells to CTL development has been hampered by the fact that most T(H)-independent responses have been demonstrated ex vivo as primary cytotoxic effectors, whereas T(H)-dependent responses generally require secondary in vitro re-stimulation for their detection. Here, we have monitored the primary and secondary responses of T(H)-dependent and T(H)-independent CTLs and find in both cases that CD4+ T cells are dispensable for primary expansion of CD8+ T cells and their differentiation into cytotoxic effectors. However, secondary CTL expansion (that is, a secondary response upon re-encounter with antigen) is wholly dependent on the presence of T(H) cells during, but not after, priming. Our results demonstrate that T-cell help is 'programmed' into CD8+ T cells during priming, conferring on these cells a hallmark of immune response memory: the capacity for functional expansion on re-encounter with antigen.

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Authors: Janssen, E. M., Lemmens, E. E., Wolfe, T., Christen, U., von Herrath, M. G., & Schoenberger, S. P.
Affiliations: La Jolla Institute for Immunology (US)
Corresponding author: Schoenberger, Stephen P.
ORCID: Janssen, Edith M.
Lemmens, Edward E.
Christen, Urs
Schoenberger, Stephen P.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2003-02
Volume: 421
Issue: 6925
Pages: 852-856
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature01441
OpenAlex: W1493822493
Cited by: 1,635
References: 28
Citations by year: 2026: 19 · 2025: 24 · 2024: 37 · 2023: 46 · 2022: 37 · 2021: 42 · 2020: 58 · 2019: 42 · 2018: 52 · 2017: 36 · 2016: 41 · 2015: 61 · 2014: 63 · 2013: 63 · 2012: 71
FWCI: 46.09
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: National Institutes of Health
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 › Immune responses and vaccinations
Keywords: CD4+ T cells, CD8+ T cells, cytotoxic T lymphocytes, T helper cells, secondary immune response, T cell memory, T cell help, cross-priming, antigen-presenting cells, T cell differentiation
MeSH terms: Animals, Antigens, Cell Line, Cytotoxicity, Immunologic, Flow Cytometry, T-Lymphocytes, Helper-Inducer, Immunologic Memory, Lymphocyte Activation, Lymphocytic choriomeningitis virus, T-Lymphocytes, Cytotoxic, Mice

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CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes

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