Modelling T-cell immunity against hepatitis C virus with liver organoids in a microfluidic coculture system
Hepatitis C virus (HCV) remains a global public health challenge with an estimated 71 million people chronically infected, with surges in new cases and no effective vaccine. New methods are needed to study the human immune response to HCV since in vivo animal models are limited and in vitro cancer c...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
The Royal Society
2022-03-01
|
| Series: | Open Biology |
| Subjects: | |
| Online Access: | https://royalsocietypublishing.org/doi/10.1098/rsob.210320 |
| _version_ | 1827957883380170752 |
|---|---|
| author | Vaishaali Natarajan Camille R. Simoneau Ann L. Erickson Nathan L. Meyers Jody L. Baron Stewart Cooper Todd C. McDevitt Melanie Ott |
| author_facet | Vaishaali Natarajan Camille R. Simoneau Ann L. Erickson Nathan L. Meyers Jody L. Baron Stewart Cooper Todd C. McDevitt Melanie Ott |
| author_sort | Vaishaali Natarajan |
| collection | DOAJ |
| description | Hepatitis C virus (HCV) remains a global public health challenge with an estimated 71 million people chronically infected, with surges in new cases and no effective vaccine. New methods are needed to study the human immune response to HCV since in vivo animal models are limited and in vitro cancer cell models often show dysregulated immune and proliferative responses. Here, we developed a CD8+ T cell and adult stem cell liver organoid system using a microfluidic chip to coculture 3D human liver organoids embedded in extracellular matrix with HLA-matched primary human T cells in suspension. We then employed automated phase contrast and immunofluorescence imaging to monitor T cell invasion and morphological changes in the liver organoids. This microfluidic coculture system supports targeted killing of liver organoids when pulsed with a peptide specific for HCV non-structural protein 3 (NS3) (KLVALGINAV) in the presence of patient-derived CD8+ T cells specific for KLVALGINAV. This demonstrates the novel potential of the coculture system to molecularly study adaptive immune responses to HCV in an in vitro setting using primary human cells. |
| first_indexed | 2024-04-09T15:27:59Z |
| format | Article |
| id | doaj.art-78e457851ade49b89befa8fa99f0a24a |
| institution | Directory Open Access Journal |
| issn | 2046-2441 |
| language | English |
| last_indexed | 2024-04-09T15:27:59Z |
| publishDate | 2022-03-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Open Biology |
| spelling | doaj.art-78e457851ade49b89befa8fa99f0a24a2023-04-28T11:07:58ZengThe Royal SocietyOpen Biology2046-24412022-03-0112310.1098/rsob.210320Modelling T-cell immunity against hepatitis C virus with liver organoids in a microfluidic coculture systemVaishaali Natarajan0Camille R. Simoneau1Ann L. Erickson2Nathan L. Meyers3Jody L. Baron4Stewart Cooper5Todd C. McDevitt6Melanie Ott7The Gladstone Institutes, San Francisco, CA, USAThe Gladstone Institutes, San Francisco, CA, USADivision of General and Transplant Hepatology, California Pacific Medical Center and Research Institute, San Francisco, CA, USAThe Gladstone Institutes, San Francisco, CA, USAUCSF Liver Center, University of California San Francisco, San Francisco, CA, USADivision of General and Transplant Hepatology, California Pacific Medical Center and Research Institute, San Francisco, CA, USAThe Gladstone Institutes, San Francisco, CA, USAThe Gladstone Institutes, San Francisco, CA, USAHepatitis C virus (HCV) remains a global public health challenge with an estimated 71 million people chronically infected, with surges in new cases and no effective vaccine. New methods are needed to study the human immune response to HCV since in vivo animal models are limited and in vitro cancer cell models often show dysregulated immune and proliferative responses. Here, we developed a CD8+ T cell and adult stem cell liver organoid system using a microfluidic chip to coculture 3D human liver organoids embedded in extracellular matrix with HLA-matched primary human T cells in suspension. We then employed automated phase contrast and immunofluorescence imaging to monitor T cell invasion and morphological changes in the liver organoids. This microfluidic coculture system supports targeted killing of liver organoids when pulsed with a peptide specific for HCV non-structural protein 3 (NS3) (KLVALGINAV) in the presence of patient-derived CD8+ T cells specific for KLVALGINAV. This demonstrates the novel potential of the coculture system to molecularly study adaptive immune responses to HCV in an in vitro setting using primary human cells.https://royalsocietypublishing.org/doi/10.1098/rsob.210320hepatitis Cliver organoidCD8+ T cellsmicrofluidics |
| spellingShingle | Vaishaali Natarajan Camille R. Simoneau Ann L. Erickson Nathan L. Meyers Jody L. Baron Stewart Cooper Todd C. McDevitt Melanie Ott Modelling T-cell immunity against hepatitis C virus with liver organoids in a microfluidic coculture system Open Biology hepatitis C liver organoid CD8+ T cells microfluidics |
| title | Modelling T-cell immunity against hepatitis C virus with liver organoids in a microfluidic coculture system |
| title_full | Modelling T-cell immunity against hepatitis C virus with liver organoids in a microfluidic coculture system |
| title_fullStr | Modelling T-cell immunity against hepatitis C virus with liver organoids in a microfluidic coculture system |
| title_full_unstemmed | Modelling T-cell immunity against hepatitis C virus with liver organoids in a microfluidic coculture system |
| title_short | Modelling T-cell immunity against hepatitis C virus with liver organoids in a microfluidic coculture system |
| title_sort | modelling t cell immunity against hepatitis c virus with liver organoids in a microfluidic coculture system |
| topic | hepatitis C liver organoid CD8+ T cells microfluidics |
| url | https://royalsocietypublishing.org/doi/10.1098/rsob.210320 |
| work_keys_str_mv | AT vaishaalinatarajan modellingtcellimmunityagainsthepatitiscviruswithliverorganoidsinamicrofluidiccoculturesystem AT camillersimoneau modellingtcellimmunityagainsthepatitiscviruswithliverorganoidsinamicrofluidiccoculturesystem AT annlerickson modellingtcellimmunityagainsthepatitiscviruswithliverorganoidsinamicrofluidiccoculturesystem AT nathanlmeyers modellingtcellimmunityagainsthepatitiscviruswithliverorganoidsinamicrofluidiccoculturesystem AT jodylbaron modellingtcellimmunityagainsthepatitiscviruswithliverorganoidsinamicrofluidiccoculturesystem AT stewartcooper modellingtcellimmunityagainsthepatitiscviruswithliverorganoidsinamicrofluidiccoculturesystem AT toddcmcdevitt modellingtcellimmunityagainsthepatitiscviruswithliverorganoidsinamicrofluidiccoculturesystem AT melanieott modellingtcellimmunityagainsthepatitiscviruswithliverorganoidsinamicrofluidiccoculturesystem |