SARS-CoV-2 spike-specific regulatory T cells (Treg) expand and develop memory in vaccine recipients suggesting a role for immune regulation in preventing severe symptoms in COVID-19
We enrolled healthy subjects that received 2 to 4 injections of mRNA-based vaccination to prevent COVID-19 months to a year from the last vaccine boost, and we found numerous SARS-CoV-2 spike-specific regulatory T cell (Treg) that developed T cell memory as effector memory T cells (TEM) and central...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Autoimmunity |
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| Online Access: | http://dx.doi.org/10.1080/08916934.2023.2259133 |
| _version_ | 1797638468591943680 |
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| author | Alessandra Franco Jaeyoon Song Christina Chambers Alessandro Sette Alba Grifoni |
| author_facet | Alessandra Franco Jaeyoon Song Christina Chambers Alessandro Sette Alba Grifoni |
| author_sort | Alessandra Franco |
| collection | DOAJ |
| description | We enrolled healthy subjects that received 2 to 4 injections of mRNA-based vaccination to prevent COVID-19 months to a year from the last vaccine boost, and we found numerous SARS-CoV-2 spike-specific regulatory T cell (Treg) that developed T cell memory as effector memory T cells (TEM) and central memory T cells (TCM). CD4+ CD25high Treg expressed the chemokine receptor CCR6 in a considerable percentage, suggesting T cell homing to the vascular endothelium, lung and gut epithelial cells and brain. Treg phenotype was different than peripherally-induced Treg (pTreg) that revert from pro-inflammatory T cells under repeated stimulatory conditions, suggesting that SARS-CoV-2 spike-specific Treg differentiated from naïve T cells in tissues where the SARS-CoV-2 spike proteins were synthetized. Twenty two of 22 subjects studied responded to vaccination developing a spike-specific CD4+ T helper (Th)1 response, and 20 of 22 developing a spike-specific CD8+ cytotoxic T cells (CTL) response. However, in vaccine recipients the expansion of spike-specific pro-inflammatory T cells was less significant than the expansion of spike-specific Treg. Effector (TEM) and central memory (TCM) Treg were numerous as early as after two vaccine doses, with no significant differences following additional vaccine boosts. In co-culture experiments under stimulatory conditions, Treg regulated naïve T cell differentiation toward a pro-inflammatory phenotype and suppressed interferon (IFN)γ production by SARS-CoV-2-specific CD4 + Th1 cells. |
| first_indexed | 2024-03-11T13:03:53Z |
| format | Article |
| id | doaj.art-e2b440770f03455092a16ddefd577924 |
| institution | Directory Open Access Journal |
| issn | 0891-6934 1607-842X |
| language | English |
| last_indexed | 2024-03-11T13:03:53Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autoimmunity |
| spelling | doaj.art-e2b440770f03455092a16ddefd5779242023-11-03T16:27:52ZengTaylor & Francis GroupAutoimmunity0891-69341607-842X2023-12-0156110.1080/08916934.2023.22591332259133SARS-CoV-2 spike-specific regulatory T cells (Treg) expand and develop memory in vaccine recipients suggesting a role for immune regulation in preventing severe symptoms in COVID-19Alessandra Franco0Jaeyoon Song1Christina Chambers2Alessandro Sette3Alba Grifoni4Department of Pediatrics, University of California San Diego, School of MedicineDepartment of Pediatrics, University of California San Diego, School of MedicineDepartment of Pediatrics, University of California San Diego, School of MedicineCenter for Autoimmunity and Inflammation, Center for Infectious Disease and Vaccine Research, La Jolla Institute for ImmunologyCenter for Autoimmunity and Inflammation, Center for Infectious Disease and Vaccine Research, La Jolla Institute for ImmunologyWe enrolled healthy subjects that received 2 to 4 injections of mRNA-based vaccination to prevent COVID-19 months to a year from the last vaccine boost, and we found numerous SARS-CoV-2 spike-specific regulatory T cell (Treg) that developed T cell memory as effector memory T cells (TEM) and central memory T cells (TCM). CD4+ CD25high Treg expressed the chemokine receptor CCR6 in a considerable percentage, suggesting T cell homing to the vascular endothelium, lung and gut epithelial cells and brain. Treg phenotype was different than peripherally-induced Treg (pTreg) that revert from pro-inflammatory T cells under repeated stimulatory conditions, suggesting that SARS-CoV-2 spike-specific Treg differentiated from naïve T cells in tissues where the SARS-CoV-2 spike proteins were synthetized. Twenty two of 22 subjects studied responded to vaccination developing a spike-specific CD4+ T helper (Th)1 response, and 20 of 22 developing a spike-specific CD8+ cytotoxic T cells (CTL) response. However, in vaccine recipients the expansion of spike-specific pro-inflammatory T cells was less significant than the expansion of spike-specific Treg. Effector (TEM) and central memory (TCM) Treg were numerous as early as after two vaccine doses, with no significant differences following additional vaccine boosts. In co-culture experiments under stimulatory conditions, Treg regulated naïve T cell differentiation toward a pro-inflammatory phenotype and suppressed interferon (IFN)γ production by SARS-CoV-2-specific CD4 + Th1 cells.http://dx.doi.org/10.1080/08916934.2023.2259133regulatory t cells (treg)vaccinesars-cov-2immune regulationt cell memory |
| spellingShingle | Alessandra Franco Jaeyoon Song Christina Chambers Alessandro Sette Alba Grifoni SARS-CoV-2 spike-specific regulatory T cells (Treg) expand and develop memory in vaccine recipients suggesting a role for immune regulation in preventing severe symptoms in COVID-19 Autoimmunity regulatory t cells (treg) vaccine sars-cov-2 immune regulation t cell memory |
| title | SARS-CoV-2 spike-specific regulatory T cells (Treg) expand and develop memory in vaccine recipients suggesting a role for immune regulation in preventing severe symptoms in COVID-19 |
| title_full | SARS-CoV-2 spike-specific regulatory T cells (Treg) expand and develop memory in vaccine recipients suggesting a role for immune regulation in preventing severe symptoms in COVID-19 |
| title_fullStr | SARS-CoV-2 spike-specific regulatory T cells (Treg) expand and develop memory in vaccine recipients suggesting a role for immune regulation in preventing severe symptoms in COVID-19 |
| title_full_unstemmed | SARS-CoV-2 spike-specific regulatory T cells (Treg) expand and develop memory in vaccine recipients suggesting a role for immune regulation in preventing severe symptoms in COVID-19 |
| title_short | SARS-CoV-2 spike-specific regulatory T cells (Treg) expand and develop memory in vaccine recipients suggesting a role for immune regulation in preventing severe symptoms in COVID-19 |
| title_sort | sars cov 2 spike specific regulatory t cells treg expand and develop memory in vaccine recipients suggesting a role for immune regulation in preventing severe symptoms in covid 19 |
| topic | regulatory t cells (treg) vaccine sars-cov-2 immune regulation t cell memory |
| url | http://dx.doi.org/10.1080/08916934.2023.2259133 |
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