Differentiation of Memory CD8 T Cells Unravel Gene Expression Pattern Common to Effector and Memory Precursors
Long-term immunological protection relies on the differentiation and maintenance of memory lymphocytes. Since the knowledge of memory generation has been centered on in vivo models of infection, there are obstacles to deep molecular analysis of differentiating subsets. Here we defined a novel in vit...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.840203/full |
| _version_ | 1811340977983455232 |
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| author | Vanessa Neitzke-Montinelli Carolina Calôba Guilherme Melo Bianca B. Frade Enzo Caramez Luciano Mazzoccoli André N. A. Gonçalves Helder I. Nakaya Helder I. Nakaya Renata M. Pereira Miriam B. F. Werneck João P. B. Viola |
| author_facet | Vanessa Neitzke-Montinelli Carolina Calôba Guilherme Melo Bianca B. Frade Enzo Caramez Luciano Mazzoccoli André N. A. Gonçalves Helder I. Nakaya Helder I. Nakaya Renata M. Pereira Miriam B. F. Werneck João P. B. Viola |
| author_sort | Vanessa Neitzke-Montinelli |
| collection | DOAJ |
| description | Long-term immunological protection relies on the differentiation and maintenance of memory lymphocytes. Since the knowledge of memory generation has been centered on in vivo models of infection, there are obstacles to deep molecular analysis of differentiating subsets. Here we defined a novel in vitro CD8 T cell activation and culture regimen using low TCR engagement and cytokines to generate differentiated cells consistent with central memory-like cells, as shown by surface phenotype, gene expression profile and lack of cytotoxic function after challenge. Our results showed an effector signature expressed by in vitro memory precursors and their plasticity under specific conditions. Moreover, memory CD8 T cells conferred long-term protection against bacterial infection and slowed in vivo tumor growth more efficiently than effector cells. This model may allow further understanding of CD8 T cell memory molecular differentiation subsets and be suited for generating cells to be used for immunotherapy. |
| first_indexed | 2024-04-13T18:50:27Z |
| format | Article |
| id | doaj.art-618a0bd1306c4679bcb6a137e9955e5c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T18:50:27Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-618a0bd1306c4679bcb6a137e9955e5c2022-12-22T02:34:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-05-011310.3389/fimmu.2022.840203840203Differentiation of Memory CD8 T Cells Unravel Gene Expression Pattern Common to Effector and Memory PrecursorsVanessa Neitzke-Montinelli0Carolina Calôba1Guilherme Melo2Bianca B. Frade3Enzo Caramez4Luciano Mazzoccoli5André N. A. Gonçalves6Helder I. Nakaya7Helder I. Nakaya8Renata M. Pereira9Miriam B. F. Werneck10João P. B. Viola11Program of Immunology and Tumor Biology, Brazilian National Cancer Institute, Instituto Nacional de Câncer (INCA), Rio de Janeiro, BrazilInstitute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, BrazilInstitute of Microbiology and Immunology, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, BrazilInstitute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, BrazilInstitute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, BrazilProgram of Immunology and Tumor Biology, Brazilian National Cancer Institute, Instituto Nacional de Câncer (INCA), Rio de Janeiro, BrazilDepartment of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, BrazilDepartment of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo (USP), São Paulo, BrazilHospital Israelita Albert Einstein, São Paulo, BrazilInstitute of Microbiology and Immunology, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, BrazilInstitute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, BrazilProgram of Immunology and Tumor Biology, Brazilian National Cancer Institute, Instituto Nacional de Câncer (INCA), Rio de Janeiro, BrazilLong-term immunological protection relies on the differentiation and maintenance of memory lymphocytes. Since the knowledge of memory generation has been centered on in vivo models of infection, there are obstacles to deep molecular analysis of differentiating subsets. Here we defined a novel in vitro CD8 T cell activation and culture regimen using low TCR engagement and cytokines to generate differentiated cells consistent with central memory-like cells, as shown by surface phenotype, gene expression profile and lack of cytotoxic function after challenge. Our results showed an effector signature expressed by in vitro memory precursors and their plasticity under specific conditions. Moreover, memory CD8 T cells conferred long-term protection against bacterial infection and slowed in vivo tumor growth more efficiently than effector cells. This model may allow further understanding of CD8 T cell memory molecular differentiation subsets and be suited for generating cells to be used for immunotherapy.https://www.frontiersin.org/articles/10.3389/fimmu.2022.840203/fullCD8 T cell differentiationimmunological memorycytotoxicityadoptive cell transferimmunotherapy |
| spellingShingle | Vanessa Neitzke-Montinelli Carolina Calôba Guilherme Melo Bianca B. Frade Enzo Caramez Luciano Mazzoccoli André N. A. Gonçalves Helder I. Nakaya Helder I. Nakaya Renata M. Pereira Miriam B. F. Werneck João P. B. Viola Differentiation of Memory CD8 T Cells Unravel Gene Expression Pattern Common to Effector and Memory Precursors Frontiers in Immunology CD8 T cell differentiation immunological memory cytotoxicity adoptive cell transfer immunotherapy |
| title | Differentiation of Memory CD8 T Cells Unravel Gene Expression Pattern Common to Effector and Memory Precursors |
| title_full | Differentiation of Memory CD8 T Cells Unravel Gene Expression Pattern Common to Effector and Memory Precursors |
| title_fullStr | Differentiation of Memory CD8 T Cells Unravel Gene Expression Pattern Common to Effector and Memory Precursors |
| title_full_unstemmed | Differentiation of Memory CD8 T Cells Unravel Gene Expression Pattern Common to Effector and Memory Precursors |
| title_short | Differentiation of Memory CD8 T Cells Unravel Gene Expression Pattern Common to Effector and Memory Precursors |
| title_sort | differentiation of memory cd8 t cells unravel gene expression pattern common to effector and memory precursors |
| topic | CD8 T cell differentiation immunological memory cytotoxicity adoptive cell transfer immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.840203/full |
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