Direct ex vivo comparison of the breadth and specificity of the T cells in the liver and peripheral blood of patients with chronic HCV infection.
The role of intrahepatic lymphocytes in the control of hepatitis C virus (HCV) infection and the pathology associated with it is not understood; most studies of the immunology of this infection use peripheral blood lymphocyte populations. To address this further, we examined in detail the IHL from H...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2001
|
| _version_ | 1797099272300134400 |
|---|---|
| author | Grabowska, A Lechner, F Klenerman, P Tighe, P Ryder, S Ball, J Thomson, B Irving, W Robins, R |
| author_facet | Grabowska, A Lechner, F Klenerman, P Tighe, P Ryder, S Ball, J Thomson, B Irving, W Robins, R |
| author_sort | Grabowska, A |
| collection | OXFORD |
| description | The role of intrahepatic lymphocytes in the control of hepatitis C virus (HCV) infection and the pathology associated with it is not understood; most studies of the immunology of this infection use peripheral blood lymphocyte populations. To address this further, we examined in detail the IHL from HCV-infected patients and controls, focusing on the antigen-specific CD8(+) T lymphocyte component. Individual T cells from needle liver biopsies and peripheral blood were isolated from patients with chronic HCV infection and examined directly ex vivo. We used RT-PCR spectratyping to compare the breadth of the T cell receptor usage in the liver in comparison with the peripheral blood, and applied MHC class I tetramer technology to investigate the numbers of HCV-specific CD8(+) cells in the two compartments. T cell receptor usage in the liver of HCV-infected patients was broad, comparable with that in the peripheral blood of the same patients. A much higher proportion of liver CD8(+) cells expressed receptors specific for HCV antigens compared with paired peripheral blood CD8(+) cells. A greater proportion of the liver tetramer-positive cells expressed the activation marker CD69, compared with those in the periphery or other CD8(+) cells in the liver. In the course of chronic HCV infection, HCV-specific CD8 cells, which have been recently activated, appear to accumulate specifically in the livers of infected patients but are present in much lower numbers in the peripheral circulation. Further studies are needed to determine the function of these cells and their role in protection and immunopathology. |
| first_indexed | 2024-03-07T05:21:25Z |
| format | Journal article |
| id | oxford-uuid:df0cfc3c-f6da-4e2a-ab10-2a52458de943 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:21:25Z |
| publishDate | 2001 |
| record_format | dspace |
| spelling | oxford-uuid:df0cfc3c-f6da-4e2a-ab10-2a52458de9432022-03-27T09:36:33ZDirect ex vivo comparison of the breadth and specificity of the T cells in the liver and peripheral blood of patients with chronic HCV infection.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:df0cfc3c-f6da-4e2a-ab10-2a52458de943EnglishSymplectic Elements at Oxford2001Grabowska, ALechner, FKlenerman, PTighe, PRyder, SBall, JThomson, BIrving, WRobins, RThe role of intrahepatic lymphocytes in the control of hepatitis C virus (HCV) infection and the pathology associated with it is not understood; most studies of the immunology of this infection use peripheral blood lymphocyte populations. To address this further, we examined in detail the IHL from HCV-infected patients and controls, focusing on the antigen-specific CD8(+) T lymphocyte component. Individual T cells from needle liver biopsies and peripheral blood were isolated from patients with chronic HCV infection and examined directly ex vivo. We used RT-PCR spectratyping to compare the breadth of the T cell receptor usage in the liver in comparison with the peripheral blood, and applied MHC class I tetramer technology to investigate the numbers of HCV-specific CD8(+) cells in the two compartments. T cell receptor usage in the liver of HCV-infected patients was broad, comparable with that in the peripheral blood of the same patients. A much higher proportion of liver CD8(+) cells expressed receptors specific for HCV antigens compared with paired peripheral blood CD8(+) cells. A greater proportion of the liver tetramer-positive cells expressed the activation marker CD69, compared with those in the periphery or other CD8(+) cells in the liver. In the course of chronic HCV infection, HCV-specific CD8 cells, which have been recently activated, appear to accumulate specifically in the livers of infected patients but are present in much lower numbers in the peripheral circulation. Further studies are needed to determine the function of these cells and their role in protection and immunopathology. |
| spellingShingle | Grabowska, A Lechner, F Klenerman, P Tighe, P Ryder, S Ball, J Thomson, B Irving, W Robins, R Direct ex vivo comparison of the breadth and specificity of the T cells in the liver and peripheral blood of patients with chronic HCV infection. |
| title | Direct ex vivo comparison of the breadth and specificity of the T cells in the liver and peripheral blood of patients with chronic HCV infection. |
| title_full | Direct ex vivo comparison of the breadth and specificity of the T cells in the liver and peripheral blood of patients with chronic HCV infection. |
| title_fullStr | Direct ex vivo comparison of the breadth and specificity of the T cells in the liver and peripheral blood of patients with chronic HCV infection. |
| title_full_unstemmed | Direct ex vivo comparison of the breadth and specificity of the T cells in the liver and peripheral blood of patients with chronic HCV infection. |
| title_short | Direct ex vivo comparison of the breadth and specificity of the T cells in the liver and peripheral blood of patients with chronic HCV infection. |
| title_sort | direct ex vivo comparison of the breadth and specificity of the t cells in the liver and peripheral blood of patients with chronic hcv infection |
| work_keys_str_mv | AT grabowskaa directexvivocomparisonofthebreadthandspecificityofthetcellsintheliverandperipheralbloodofpatientswithchronichcvinfection AT lechnerf directexvivocomparisonofthebreadthandspecificityofthetcellsintheliverandperipheralbloodofpatientswithchronichcvinfection AT klenermanp directexvivocomparisonofthebreadthandspecificityofthetcellsintheliverandperipheralbloodofpatientswithchronichcvinfection AT tighep directexvivocomparisonofthebreadthandspecificityofthetcellsintheliverandperipheralbloodofpatientswithchronichcvinfection AT ryders directexvivocomparisonofthebreadthandspecificityofthetcellsintheliverandperipheralbloodofpatientswithchronichcvinfection AT ballj directexvivocomparisonofthebreadthandspecificityofthetcellsintheliverandperipheralbloodofpatientswithchronichcvinfection AT thomsonb directexvivocomparisonofthebreadthandspecificityofthetcellsintheliverandperipheralbloodofpatientswithchronichcvinfection AT irvingw directexvivocomparisonofthebreadthandspecificityofthetcellsintheliverandperipheralbloodofpatientswithchronichcvinfection AT robinsr directexvivocomparisonofthebreadthandspecificityofthetcellsintheliverandperipheralbloodofpatientswithchronichcvinfection |