Type-1 regulatory T cells are critical for curative immunotherapy outcomes Article Swipe
Ping Zhang
,
Kate H. Gartlan
,
Simone A. Minnie
,
Albert C. Yeh
,
Shuichiro Takahashi
,
Erden Atilla
,
Nicole S Nemychenkov
,
Julie R Boiko
,
Christine R. Schmidt
,
Samuel R.W. Legg
,
Tomoko Sekiguchi
,
Kathleen S. Ensbey
,
Motoko Koyama
,
Scott N. Furlan
,
Geoffrey R. Hill
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.4049/jimmunol.210.supp.173.11
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.4049/jimmunol.210.supp.173.11
IL-10 producing CD4+ type-1 regulatory T cells (Tr1) mediate immune tolerance during chronic infection, autoimmunity, and transplantation. We previously demonstrated that eomesodermin (Eomes) promotes Tr1 cell (Eomes+IL-10+) development after allogenic bone marrow transplantation (alloBMT). Here we define the differentiation trajectory of Tr1 cells and the functional states therein. Eomes−IL-10−, Eomes+IL-10− and Eomes+IL-10+ subsets (defined by mCherry and GFP expression respectively) were FACS sorted after alloBMT and transferred into secondary recipients. Eomes+IL-10+ T cells were stable in phenotype after transfer while the Eomes+IL-10− T cell subset differentiated into Eomes+IL-10+ Tr1 cells. Tr1 differentiation was associated with progressive enrichment for cytotoxicity (Perforin, Nkg7, Granzyme K, Tnfrsf9), immune regulatory (IR) (Tim-3, Lag3, Tox, Nr4a2) and chemokine (Ccl3, Ccl4, Ccl5) RNA expression. Equivalent IR, cytotoxic and cytokine/chemokine expression was confirmed at a protein level. The conditional deletion of Eomes in CD4 T cells prevented Tr1 differentiation and resulted in impaired cytotoxicity in vivo, the accumulation of donor CD11c+ dendritic cells, mixed donor chimerism and leukemia relapse, consistent with a critical role for this lineage in tolerance, engraftment and graft-versus-leukemia effects. The deletion of Eomes from CD19-targeted chimeric antigen receptor (CAR) T cells, reduced cytotoxic molecule expression (perforin, granzyme A/B) in CD4 CAR T cells and resulted in immune escape due to CD19 antigen loss in leukemia cells. In sum, Tr1 cells mediate critical Eomes-dependent cytotoxic and regulatory function that are critical for curative immunotherapy outcomes.
Related Topics
Concepts
Cytotoxic T cell
Biology
Granzyme B
Granzyme
Immunology
Immune system
Perforin
Cancer research
T cell
Cell biology
CD8
Biochemistry
In vitro
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.4049/jimmunol.210.supp.173.11
- https://journals.aai.org/jimmunol/article-pdf/210/1_Supplement/173.11/1633818/173_11.pdf
- OA Status
- bronze
- Cited By
- 1
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4385687082
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4385687082Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.4049/jimmunol.210.supp.173.11Digital Object Identifier
- Title
-
Type-1 regulatory T cells are critical for curative immunotherapy outcomesWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-05-01Full publication date if available
- Authors
-
Ping Zhang, Kate H. Gartlan, Simone A. Minnie, Albert C. Yeh, Shuichiro Takahashi, Erden Atilla, Nicole S Nemychenkov, Julie R Boiko, Christine R. Schmidt, Samuel R.W. Legg, Tomoko Sekiguchi, Kathleen S. Ensbey, Motoko Koyama, Scott N. Furlan, Geoffrey R. HillList of authors in order
- Landing page
-
https://doi.org/10.4049/jimmunol.210.supp.173.11Publisher landing page
- PDF URL
-
https://journals.aai.org/jimmunol/article-pdf/210/1_Supplement/173.11/1633818/173_11.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
bronzeOpen access status per OpenAlex
- OA URL
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https://journals.aai.org/jimmunol/article-pdf/210/1_Supplement/173.11/1633818/173_11.pdfDirect OA link when available
- Concepts
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Cytotoxic T cell, Biology, Granzyme B, Granzyme, Immunology, Immune system, Perforin, Cancer research, T cell, Cell biology, CD8, Biochemistry, In vitroTop concepts (fields/topics) attached by OpenAlex
- Cited by
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1Total citation count in OpenAlex
- Citations by year (recent)
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2024: 1Per-year citation counts (last 5 years)
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| primary_location.pdf_url | https://journals.aai.org/jimmunol/article-pdf/210/1_Supplement/173.11/1633818/173_11.pdf |
| primary_location.version | publishedVersion |
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| primary_location.license_id | |
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| primary_location.is_published | True |
| primary_location.raw_source_name | The Journal of Immunology |
| primary_location.landing_page_url | https://doi.org/10.4049/jimmunol.210.supp.173.11 |
| publication_date | 2023-05-01 |
| publication_year | 2023 |
| referenced_works_count | 0 |
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