Repetitive antigen stimulation in the periphery dictates the composition and recall responses of brain-resident memory CD8+ T cells
Summary: The human brain harbors virus-specific, tissue-resident memory (TRM) CD8+ T cells. However, the impact of repeated peripheral viral infection on the generation, phenotype, localization, and recall responses of brain TRM remains elusive. Here, utilizing two murine models of peripheral viral...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472500018X |
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| author | Madison R. Mix Stephanie van de Wall Mohammad Heidarian Elizabeth A. Escue Cori E. Fain Lecia L. Pewe Lisa S. Hancox Sahaana A. Arumugam Cassie M. Sievers Vladimir P. Badovinac John T. Harty |
| author_facet | Madison R. Mix Stephanie van de Wall Mohammad Heidarian Elizabeth A. Escue Cori E. Fain Lecia L. Pewe Lisa S. Hancox Sahaana A. Arumugam Cassie M. Sievers Vladimir P. Badovinac John T. Harty |
| author_sort | Madison R. Mix |
| collection | DOAJ |
| description | Summary: The human brain harbors virus-specific, tissue-resident memory (TRM) CD8+ T cells. However, the impact of repeated peripheral viral infection on the generation, phenotype, localization, and recall responses of brain TRM remains elusive. Here, utilizing two murine models of peripheral viral infection, we demonstrate that circulating memory CD8+ T cells with previous antigen exposure exhibit a markedly reduced capacity to form brain TRM compared to naive CD8+ T cells. Repetitively stimulated brain TRM also demonstrate differential inhibitory receptor expression, preserved functionality, and divergent localization patterns compared to primary memory counterparts. Despite these differences, repetitively stimulated brain TRM provide similar protection against intracranial infection as primary populations with superior recall-based recruitment of peripheral lymphocytes. As CD8+ T cells may distinctly seed the brain with each repeated infection of the same host, these findings point to heterogeneity in the brain TRM pool that is dictated by prior peripheral antigen stimulation history. |
| format | Article |
| id | doaj-art-0c396092d574458ca95e3e94597c4157 |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-0c396092d574458ca95e3e94597c41572025-02-04T04:10:23ZengElsevierCell Reports2211-12472025-02-01442115247Repetitive antigen stimulation in the periphery dictates the composition and recall responses of brain-resident memory CD8+ T cellsMadison R. Mix0Stephanie van de Wall1Mohammad Heidarian2Elizabeth A. Escue3Cori E. Fain4Lecia L. Pewe5Lisa S. Hancox6Sahaana A. Arumugam7Cassie M. Sievers8Vladimir P. Badovinac9John T. Harty10Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Medical Scientist Training Program, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Interdisciplinary Graduate Program in Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USADepartment of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USADepartment of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Experimental Pathology Graduate Program, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USADepartment of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Experimental Pathology Graduate Program, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USADepartment of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USADepartment of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USADepartment of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USADepartment of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Medical Scientist Training Program, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Interdisciplinary Graduate Program in Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USADepartment of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USADepartment of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Medical Scientist Training Program, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Interdisciplinary Graduate Program in Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Experimental Pathology Graduate Program, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USADepartment of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Medical Scientist Training Program, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Interdisciplinary Graduate Program in Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Experimental Pathology Graduate Program, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Corresponding authorSummary: The human brain harbors virus-specific, tissue-resident memory (TRM) CD8+ T cells. However, the impact of repeated peripheral viral infection on the generation, phenotype, localization, and recall responses of brain TRM remains elusive. Here, utilizing two murine models of peripheral viral infection, we demonstrate that circulating memory CD8+ T cells with previous antigen exposure exhibit a markedly reduced capacity to form brain TRM compared to naive CD8+ T cells. Repetitively stimulated brain TRM also demonstrate differential inhibitory receptor expression, preserved functionality, and divergent localization patterns compared to primary memory counterparts. Despite these differences, repetitively stimulated brain TRM provide similar protection against intracranial infection as primary populations with superior recall-based recruitment of peripheral lymphocytes. As CD8+ T cells may distinctly seed the brain with each repeated infection of the same host, these findings point to heterogeneity in the brain TRM pool that is dictated by prior peripheral antigen stimulation history.http://www.sciencedirect.com/science/article/pii/S221112472500018XCP: NeuroscienceCP: Immunology |
| spellingShingle | Madison R. Mix Stephanie van de Wall Mohammad Heidarian Elizabeth A. Escue Cori E. Fain Lecia L. Pewe Lisa S. Hancox Sahaana A. Arumugam Cassie M. Sievers Vladimir P. Badovinac John T. Harty Repetitive antigen stimulation in the periphery dictates the composition and recall responses of brain-resident memory CD8+ T cells Cell Reports CP: Neuroscience CP: Immunology |
| title | Repetitive antigen stimulation in the periphery dictates the composition and recall responses of brain-resident memory CD8+ T cells |
| title_full | Repetitive antigen stimulation in the periphery dictates the composition and recall responses of brain-resident memory CD8+ T cells |
| title_fullStr | Repetitive antigen stimulation in the periphery dictates the composition and recall responses of brain-resident memory CD8+ T cells |
| title_full_unstemmed | Repetitive antigen stimulation in the periphery dictates the composition and recall responses of brain-resident memory CD8+ T cells |
| title_short | Repetitive antigen stimulation in the periphery dictates the composition and recall responses of brain-resident memory CD8+ T cells |
| title_sort | repetitive antigen stimulation in the periphery dictates the composition and recall responses of brain resident memory cd8 t cells |
| topic | CP: Neuroscience CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S221112472500018X |
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