Cutting Edge: Re-evaluating the In Vivo Cytokine Responses of CD8+ T Cells during Primary and Secondary Viral Infections

Liu, Fei; Whitton, J Lindsay

doi:10.4049/jimmunol.174.10.5936

Cited by 149T-cell and B-cell ImmunologyImmunotherapy and Immune ResponsesHIV Research and Treatment

Cutting Edge: Re-evaluating the In Vivo Cytokine Responses of CD8+ T Cells during Primary and Secondary Viral Infections

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Liu, Fei, Whitton, J Lindsay·2005·The Journal of Immunology

DOI 10.4049/jimmunol.174.10.5936

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Abstract

Virus-specific CD8+ T cells produce IFN-γ after Ag contact and, in the absence of this cytokine, the host often cannot eradicate infection. However, our ability to identify cells that are actively expressing this critical effector function in vivo is limited, because the protein is rapidly secreted. In this study, we describe a simple approach that circumvents the need for ex vivo Ag stimulation and allows the enumeration of CD8+ T cells that are actively synthesizing IFN-γ in vivo during primary and secondary virus infections. The proportion of Ag-specific primary CD8+ T cells producing IFN-γ peaks at 5 days postinfection, when the T cell population is still expanding exponentially. In vivo IFN-γ synthesis by memory cells is explosive, peaking at ∼12 h after secondary infection and terminating hours thereafter. This technique will be useful when evaluating in vivo immune cell activity in many situations, including a variety of noninfectious (e.g., autoimmune) diseases.

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BrefA or monensin can be administered to mice during an active immune response, with mice euthanized shortly after administration and immediate analysis of cytokine production directly ex vivo.
“In addition, BrefA or monensin can be administered to mice during an active immune response, with mice euthanized shortly after administration and immediate analysis of cytokine production directly ex vivo [234].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [234]
The section on BFA inoculation during virus infection reports injecting infected mice with BFA, sacrificing them six hours later, and analyzing splenocytes by direct ICCS. The direct-ICCS methods describe rapid processing after harvest. The passages support the procedure for BFA, but not the claim that monensin can be used in the same way. (LLM, conf=0.89)
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Authors: Liu, F., & Whitton, J. L.
Affiliations: Scripps Research Institute (US)
ORCID: Liu, Fei
Whitton, J Lindsay
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 2005-05
Volume: 174
Issue: 10
Pages: 5936-5940
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.174.10.5936
OpenAlex: W2132668257
Cited by: 149
References: 16
Citations by year: 2026: 2 · 2025: 5 · 2024: 8 · 2022: 2 · 2021: 5 · 2020: 8 · 2019: 5 · 2018: 10 · 2017: 5 · 2016: 8 · 2015: 6 · 2014: 11 · 2013: 9 · 2012: 8
FWCI: 3.31
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Institute of Allergy and Infectious Diseases (R-01 AI-27028, R-01 AI-52351)
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 › Virology › HIV Research and Treatment
Keywords: CD8+ T cells, interferon-gamma, viral infection, primary infection, secondary infection, memory T cells, T cell expansion, virus-specific T cells, cytokine production
MeSH terms: Animals, Immunization, Secondary, Immunologic Memory, Injections, Intraperitoneal, Interferon-gamma, Listeriosis, Listeria monocytogenes, Lymphocyte Activation, Lymphocytic Choriomeningitis, Lymphocytic choriomeningitis virus, Mice, Inbred C57BL, Vaccinia, Vaccinia virus, Cytokines, Mice, Knockout, CD8-Positive T-Lymphocytes, Lymphocyte Count, Epitopes, T-Lymphocyte, Brefeldin A, Mice

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Cutting Edge: Re-evaluating the In Vivo Cytokine Responses of CD8+ T Cells during Primary and Secondary Viral Infections

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