Memory T cells possess an innate-like function in local protection from mucosal infection
Open accessAbstract
Mucosal infections pose a significant global health burden. Antigen-specific tissue-resident T cells are critical to maintaining barrier immunity. Previous studies in the context of systemic infection suggest that memory CD8+ T cells may also provide innate-like protection against antigenically unrelated pathogens independent of T cell receptor engagement. Whether bystander T cell activation is also an important defense mechanism in the mucosa is poorly understood. Here, we investigated whether innate-like memory CD8+ T cells could protect against a model mucosal virus infection, herpes simplex virus 2 (HSV-2). We found that immunization with an irrelevant antigen delayed disease progression from lethal HSV-2 challenge, suggesting that memory CD8+ T cells may mediate protection despite the lack of antigen specificity. Upon HSV-2 infection, we observed an early infiltration, rather than substantial local proliferation, of antigen-nonspecific CD8+ T cells, which became bystander-activated only within the infected mucosal tissue. Critically, we show that bystander-activated CD8+ T cells are sufficient to reduce early viral burden after HSV-2 infection. Finally, local cytokine cues within the tissue microenvironment after infection were sufficient for bystander activation of mucosal tissue memory CD8+ T cells from mice and humans. Altogether, our findings suggest that local bystander activation of CD8+ memory T cells contributes a fast and effective innate-like response to infection in mucosal tissue.
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All skin-resident T cells are pre-activated T cells with effector/memory-like phenotypes, which could be activated in an innate fashion by alterations of molecular cues of the local tissue they reside in.
“All skin-resident T cells are pre-activated T cells with effector/memory-like phenotypes, which could be activated in an innate fashion by alterations of molecular cues of the local tissue they reside in.26,27,28,29,30,31,32”
From Skin-resident T cells play an important role in controlling skin colonization of Candidozyma (Candida) auris (2026) · cites this paper as [31]
The Results section on human mucosal tissue memory CD8+ T cells reports that local cytokines can trigger innate-like bystander activation. The paper does not establish that all skin-resident T cells are pre-activated or have effector/memory-like phenotypes; its findings concern memory CD8+ T cells, primarily in mucosal tissue. Page numbers are unavailable in our copy. (LLM, conf=0.88)
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- Authors
- Arkatkar, T., Davé, V., Cruz Talavera, I., Graham, J. B., Swarts, J. L., Hughes, S. M., Bell, T. A., Hock, P., Farrington, J., Shaw, G. D., Kirby, A., Fialkow, M., Huang, M.-L., Jerome, K. R., Ferris, M. T., Hladik, F., Schiffer, J. T., Prlic, M., & Lund, J. M.
- Affiliations
- Fred Hutch Cancer Center (US)
- University of Washington (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Lund, Jennifer M.
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2023-05-15
- Volume
- 133
- Issue
- 10
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC10178838
- OpenAlex
- W4360600559
- Cited by
- 25
- References
- 58
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 7 · 2023: 5
- FWCI
- 2.74
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Clinical Investigation (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (R01 AI121129,R01 AI131914,R21 AI152559,U19 AI100625)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- memory CD8+ T cells, bystander T cell activation, mucosal immunity, herpes simplex virus type 2, barrier immunity, tissue-resident T cells
- MeSH terms
- Memory T Cells, Animals, Herpes Simplex, Humans, Immunization, Immunologic Memory, Herpesvirus 2, Human, CD8-Positive T-Lymphocytes, 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 ›
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