The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Skin-resident memory CD4+ T cells enhance protection against Leishmania major infection
Open accessAbstract
Leishmaniasis causes a significant disease burden worldwide. Although Leishmania-infected patients become refractory to reinfection after disease resolution, effective immune protection has not yet been achieved by human vaccines. Although circulating Leishmania-specific T cells are known to play a critical role in immunity, the role of memory T cells present in peripheral tissues has not been explored. Here, we identify a population of skin-resident Leishmania-specific memory CD4+ T cells. These cells produce IFN-γ and remain resident in the skin when transplanted by skin graft onto naive mice. They function to recruit circulating T cells to the skin in a CXCR3-dependent manner, resulting in better control of the parasites. Our findings are the first to demonstrate that CD4+ TRM cells form in response to a parasitic infection, and indicate that optimal protective immunity to Leishmania, and thus the success of a vaccine, may depend on generating both circulating and skin-resident memory T cells.
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“Th17 cells play a critical role in host defense against C. albicans [30–33,36], whereas Th1 cells protect the host against reinfection from HSV and L. major [34,35].”
From The Emerging Fungal Pathogen Candida auris Induces IFNγ to Colonize the Skin (2025) · cites this paper as [35]
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“Effector T cells play a critical role in the host’s defense during reinfection with C. albicans, Staphylococcus aureus, Leishmania major, and HSV [28,30–35].”
From The Emerging Fungal Pathogen Candida auris Induces IFNγ to Colonize the Skin (2025) · cites this paper as [35]
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“Furthermore, previous findings from our laboratory [16] and others [35] suggest that other cell types, such as keratinocytes and NK cells, also express IL-17A and IFNγ, respectively.”
From The Emerging Fungal Pathogen Candida auris Induces IFNγ to Colonize the Skin (2025) · cites this paper as [35]
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Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
Preferential Localization of Effector Memory Cells in Nonlymphoid Tissue
Masopust, D., Vezys, V., Marzo, A. L., & Lefrançois, L. (2001) · Science · doi:10.1126/science.1058867 · Cited by 1,952 · cited 2×
“In addition to circulating memory T cells, an additional memory T cell subset resides in the tissues as resident memory T cells (TRM; Kim et al., 1999; Hogan et al., 2001a; Masopust et al., 2001; Clark et al., 2006; Gebhardt et al., 2009; Wakim et al., 2010; Hofmann and Pircher, 2011; Jiang et al., 2012; Mackay et al.…”
BackgroundCD4+CD25+ regulatory T cells control Leishmania major persistence and immunity
Belkaid, Y., Piccirillo, C. A., Méndez, S., Shevach, E. M., & Sacks, D. L. (2002) · Nature · doi:10.1038/nature01152 · Cited by 1,726
Gebhardt, T., Wakim, L. M., Eidsmo, L., Reading, P. C., Heath, W. R., & Carbone, F. R. (2009) · Nature Immunology · doi:10.1038/ni.1718 · Cited by 1,157
Skin infection generates non-migratory memory CD8+ TRM cells providing global skin immunity
Jiang, X., Clark, R. A., Liu, L., Wagers, A. J., Fuhlbrigge, R. C., & Kupper, T. S. (2012) · Nature · doi:10.1038/nature10851 · Cited by 883
Dutton, R. W., Bradley, L. M., & Swain, S. L. (1998) · Annual Review of Immunology · doi:10.1146/annurev.immunol.16.1.201 · Cited by 832
The Vast Majority of CLA+ T Cells Are Resident in Normal Skin
Clark, R. A., Chong, B., Mirchandani, N., Brinster, N. K., Yamanaka, K.-I., Dowgiert, R. K., & Kupper, T. S. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.7.4431 · Cited by 796
Resident memory CD8 T cells trigger protective innate and adaptive immune responses
Schenkel, J. M., Fraser, K. A., Beura, L. K., Pauken, K. E., Vezys, V., & Masopust, D. (2014) · Science · doi:10.1126/science.1254536 · Cited by 731
Sensing and alarm function of resident memory CD8+ T cells
Schenkel, J., Fraser, K. A., Vezys, V., & Masopust, D. (2013) · Nature Immunology · doi:10.1038/ni.2568 · Cited by 648
Teijaro, J. R., Turner, D., Pham, Q., Wherry, E. J., Lefrançois, L., & Farber, D. L. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1102243 · Cited by 641
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Human T cell development, localization, and function throughout life
Kumar, B. V., Connors, T. J., & Farber, D. L. (2018) · Immunity · doi:10.1016/j.immuni.2018.01.007 · Cited by 1,257
Tissue-resident memory T cells: local specialists in immune defence
Mueller, S. N., & Mackay, L. K. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2015.3 · Cited by 1,006
CD49a Expression Defines Tissue-Resident CD8 + T Cells Poised for Cytotoxic Function in Human Skin
Cheuk, S., Schlums, H., Gallais Sérézal, I., Martini, E., Chiang, S. C., Marquardt, N., Gibbs, A., Detlofsson, E., Introini, A., Forkel, M., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.01.009 · Cited by 678
The multifaceted role of CD4+ T cells in CD8+ T cell memory
Laidlaw, B. J., Craft, J. E., & Kaech, S. M. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2015.10 · Cited by 657
Tissue-Resident T Cells and Other Resident Leukocytes
Masopust, D., & Soerens, A. G. (2019) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042617-053214 · Cited by 608
Metadata
- Authors
- Glennie, N. D., Yeramilli, V. A., Beiting, D. P., Volk, S. W., Weaver, C. T., & Scott, P.
- Affiliations
- University of Pennsylvania (US)
- University of Alabama at Birmingham (US)
- Corresponding author
- Scott, Phillip
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2015-07-27
- Volume
- 212
- Issue
- 9
- Pages
- 1405-1414
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC4548053
- OpenAlex
- W2162538566
- Cited by
- 204
- References
- 41
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 12 · 2023: 14 · 2022: 14 · 2021: 29 · 2020: 21 · 2019: 21 · 2018: 26 · 2017: 22 · 2016: 20 · 2015: 5
- FWCI
- 26.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- 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)
- Funders
- National Institute of Allergy and Infectious Diseases (R21AI110869, T32AI007532)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- Leishmania major, cutaneous leishmaniasis, skin-resident memory T cells, CD4+ T cells, interferon-gamma, CXCR3, skin grafting, protective immunity, leishmaniasis vaccine, parasite control
- MeSH terms
- Animals, Humans, Immunologic Memory, Interferon-gamma, Mice, Transgenic, Skin, CD4-Positive T-Lymphocytes, Leishmaniasis, Cutaneous, Leishmania major, Mice, Receptors, CXCR3
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