Clonally Focused Public and Private T Cells in Resected Brain Tissue From Surgeries to Treat Children With Intractable Seizures
Using a targeted transcriptomics approach, we have analyzed resected brain tissue from a cohort of 53 pediatric epilepsy surgery cases, and have found that there is a spectrum of involvement of both the innate and adaptive immune systems as evidenced by the differential expression of immune-specific...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.664344/full |
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| author | Julia W. Chang Samuel D. Reyes Emmanuelle Faure-Kumar Sandi K. Lam Michael W. Lawlor Richard J. Leventer Sean M. Lew Paul J. Lockhart Kathryn Pope Howard L. Weiner Noriko Salamon Harry V. Vinters Gary W. Mathern Aria Fallah Aria Fallah Geoffrey C. Owens |
| author_facet | Julia W. Chang Samuel D. Reyes Emmanuelle Faure-Kumar Sandi K. Lam Michael W. Lawlor Richard J. Leventer Sean M. Lew Paul J. Lockhart Kathryn Pope Howard L. Weiner Noriko Salamon Harry V. Vinters Gary W. Mathern Aria Fallah Aria Fallah Geoffrey C. Owens |
| author_sort | Julia W. Chang |
| collection | DOAJ |
| description | Using a targeted transcriptomics approach, we have analyzed resected brain tissue from a cohort of 53 pediatric epilepsy surgery cases, and have found that there is a spectrum of involvement of both the innate and adaptive immune systems as evidenced by the differential expression of immune-specific genes in the affected brain tissue. The specimens with the highest expression of immune-specific genes were from two Rasmussen encephalitis cases, which is known to be a neuro-immunological disease, but also from tuberous sclerosis complex (TSC), focal cortical dysplasia, and hemimegalencephaly surgery cases. We obtained T cell receptor (TCR) Vβ chain sequence data from brain tissue and blood from patients with the highest levels of T cell transcripts. The clonality indices and the frequency of the top 50 Vβ clonotypes indicated that T cells in the brain were clonally restricted. The top 50 Vβ clonotypes comprised both public and private (patient specific) clonotypes, and the TCR Vβ chain third complementarity region (CDR3) of the most abundant public Vβ clonotype in each brain sample was strikingly similar to a CDR3 that recognizes an immunodominant epitope in either human cytomegalovirus or Epstein Barr virus, or influenza virus A. We found that the frequency of 14 of the top 50 brain Vβ clonotypes from a TSC surgery case had significantly increased in brain tissue removed to control recurrent seizures 11 months after the first surgery. Conversely, we found that the frequency in the blood of 18 of the top 50 brain clonotypes from a second TSC patient, who was seizure free, had significantly decreased 5 months after surgery indicating that T cell clones found in the brain had contracted in the periphery after removal of the brain area associated with seizure activity and inflammation. However, the frequency of a public and a private clonotype significantly increased in the brain after seizures recurred and the patient underwent a second surgery. Combined single cell gene expression and TCR sequencing of brain-infiltrating leukocytes from the second surgery showed that the two clones were CD8 effector T cells, indicating that they are likely to be pathologically relevant. |
| first_indexed | 2024-12-16T12:39:46Z |
| format | Article |
| id | doaj.art-06fc4d740dee4ce39fe3cd169ded8032 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-16T12:39:46Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-06fc4d740dee4ce39fe3cd169ded80322022-12-21T22:31:26ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-04-011210.3389/fimmu.2021.664344664344Clonally Focused Public and Private T Cells in Resected Brain Tissue From Surgeries to Treat Children With Intractable SeizuresJulia W. Chang0Samuel D. Reyes1Emmanuelle Faure-Kumar2Sandi K. Lam3Michael W. Lawlor4Richard J. Leventer5Sean M. Lew6Paul J. Lockhart7Kathryn Pope8Howard L. Weiner9Noriko Salamon10Harry V. Vinters11Gary W. Mathern12Aria Fallah13Aria Fallah14Geoffrey C. Owens15Department of Neurosurgery, David Geffen School of Medicine at the University of California, Los Angeles, CA, United StatesDepartment of Neurosurgery, David Geffen School of Medicine at the University of California, Los Angeles, CA, United StatesDepartment of Medicine: Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, CA, United StatesDepartment of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Ann & Robert H. Lurie Children’s Hospital, Chicago, IL, United StatesDepartment of Pathology, Medical College of Wisconsin, Children’s Hospital of Wisconsin, Milwaukee, WI, United StatesMurdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC, AustraliaDepartment of Neurosurgery, Medical College of Wisconsin, Children’s Hospital of Wisconsin, Milwaukee, WI, United StatesMurdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC, AustraliaMurdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC, AustraliaDepartment of Pediatric Neurosurgery, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, United StatesDepartment of Radiological Sciences, David Geffen School of Medicine at the University of California, Los Angeles, CA, United StatesDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at the University of California, Los Angeles, CA, United StatesDepartment of Neurosurgery, David Geffen School of Medicine at the University of California, Los Angeles, CA, United StatesDepartment of Neurosurgery, David Geffen School of Medicine at the University of California, Los Angeles, CA, United States0Mattel Children’s Hospital, David Geffen School of Medicine at the University of California, Los Angeles, CA, United StatesDepartment of Neurosurgery, David Geffen School of Medicine at the University of California, Los Angeles, CA, United StatesUsing a targeted transcriptomics approach, we have analyzed resected brain tissue from a cohort of 53 pediatric epilepsy surgery cases, and have found that there is a spectrum of involvement of both the innate and adaptive immune systems as evidenced by the differential expression of immune-specific genes in the affected brain tissue. The specimens with the highest expression of immune-specific genes were from two Rasmussen encephalitis cases, which is known to be a neuro-immunological disease, but also from tuberous sclerosis complex (TSC), focal cortical dysplasia, and hemimegalencephaly surgery cases. We obtained T cell receptor (TCR) Vβ chain sequence data from brain tissue and blood from patients with the highest levels of T cell transcripts. The clonality indices and the frequency of the top 50 Vβ clonotypes indicated that T cells in the brain were clonally restricted. The top 50 Vβ clonotypes comprised both public and private (patient specific) clonotypes, and the TCR Vβ chain third complementarity region (CDR3) of the most abundant public Vβ clonotype in each brain sample was strikingly similar to a CDR3 that recognizes an immunodominant epitope in either human cytomegalovirus or Epstein Barr virus, or influenza virus A. We found that the frequency of 14 of the top 50 brain Vβ clonotypes from a TSC surgery case had significantly increased in brain tissue removed to control recurrent seizures 11 months after the first surgery. Conversely, we found that the frequency in the blood of 18 of the top 50 brain clonotypes from a second TSC patient, who was seizure free, had significantly decreased 5 months after surgery indicating that T cell clones found in the brain had contracted in the periphery after removal of the brain area associated with seizure activity and inflammation. However, the frequency of a public and a private clonotype significantly increased in the brain after seizures recurred and the patient underwent a second surgery. Combined single cell gene expression and TCR sequencing of brain-infiltrating leukocytes from the second surgery showed that the two clones were CD8 effector T cells, indicating that they are likely to be pathologically relevant.https://www.frontiersin.org/articles/10.3389/fimmu.2021.664344/fullT cell receptorepilepsyRasmussen encephalitisfocal cortical dysplasiatuberous sclerosis complex |
| spellingShingle | Julia W. Chang Samuel D. Reyes Emmanuelle Faure-Kumar Sandi K. Lam Michael W. Lawlor Richard J. Leventer Sean M. Lew Paul J. Lockhart Kathryn Pope Howard L. Weiner Noriko Salamon Harry V. Vinters Gary W. Mathern Aria Fallah Aria Fallah Geoffrey C. Owens Clonally Focused Public and Private T Cells in Resected Brain Tissue From Surgeries to Treat Children With Intractable Seizures Frontiers in Immunology T cell receptor epilepsy Rasmussen encephalitis focal cortical dysplasia tuberous sclerosis complex |
| title | Clonally Focused Public and Private T Cells in Resected Brain Tissue From Surgeries to Treat Children With Intractable Seizures |
| title_full | Clonally Focused Public and Private T Cells in Resected Brain Tissue From Surgeries to Treat Children With Intractable Seizures |
| title_fullStr | Clonally Focused Public and Private T Cells in Resected Brain Tissue From Surgeries to Treat Children With Intractable Seizures |
| title_full_unstemmed | Clonally Focused Public and Private T Cells in Resected Brain Tissue From Surgeries to Treat Children With Intractable Seizures |
| title_short | Clonally Focused Public and Private T Cells in Resected Brain Tissue From Surgeries to Treat Children With Intractable Seizures |
| title_sort | clonally focused public and private t cells in resected brain tissue from surgeries to treat children with intractable seizures |
| topic | T cell receptor epilepsy Rasmussen encephalitis focal cortical dysplasia tuberous sclerosis complex |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.664344/full |
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