CD39 Expression identifies terminally exhausted CD8+ T cells
Exhausted T cells express multiple co-inhibitory molecules that impair their function and limit immunity to chronic viral infection. Defining novel markers of exhaustion is important both for identifying and potentially reversing T cell exhaustion. Herein, we show that the ectonucleotidse CD39 is a...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Public Library of Science
2015
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| _version_ | 1797065269522202624 |
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| author | Gupta, P Godec, J Wolski, D Adland, E Yates, K Pauken, K Cosgrove, C Ledderose, C Junger, W Robson, S Wherry, E Alter, G Goulder, P Klenerman, P Sharpe, A Lauer, G Haining, W |
| author_facet | Gupta, P Godec, J Wolski, D Adland, E Yates, K Pauken, K Cosgrove, C Ledderose, C Junger, W Robson, S Wherry, E Alter, G Goulder, P Klenerman, P Sharpe, A Lauer, G Haining, W |
| author_sort | Gupta, P |
| collection | OXFORD |
| description | Exhausted T cells express multiple co-inhibitory molecules that impair their function and limit immunity to chronic viral infection. Defining novel markers of exhaustion is important both for identifying and potentially reversing T cell exhaustion. Herein, we show that the ectonucleotidse CD39 is a marker of exhausted CD8+ T cells. CD8+ T cells specific for HCV or HIV express high levels of CD39, but those specific for EBV and CMV do not. CD39 expressed by CD8+ T cells in chronic infection is enzymatically active, co-expressed with PD-1, marks cells with a transcriptional signature of T cell exhaustion and correlates with viral load in HIV and HCV. In the mouse model of chronic Lymphocytic Choriomeningitis Virus infection, virus-specific CD8+ T cells contain a population of CD39high CD8+ T cells that is absent in functional memory cells elicited by acute infection. This CD39high CD8+ T cell population is enriched for cells with the phenotypic and functional profile of terminal exhaustion. These findings provide a new marker of T cell exhaustion, and implicate the purinergic pathway in the regulation of T cell exhaustion. |
| first_indexed | 2024-03-06T21:26:14Z |
| format | Journal article |
| id | oxford-uuid:432f6320-bd49-406a-be0f-a3cea24c20de |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:26:14Z |
| publishDate | 2015 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:432f6320-bd49-406a-be0f-a3cea24c20de2022-03-26T14:53:57ZCD39 Expression identifies terminally exhausted CD8+ T cellsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:432f6320-bd49-406a-be0f-a3cea24c20deEnglishSymplectic Elements at OxfordPublic Library of Science2015Gupta, PGodec, JWolski, DAdland, EYates, KPauken, KCosgrove, CLedderose, CJunger, WRobson, SWherry, EAlter, GGoulder, PKlenerman, PSharpe, ALauer, GHaining, WExhausted T cells express multiple co-inhibitory molecules that impair their function and limit immunity to chronic viral infection. Defining novel markers of exhaustion is important both for identifying and potentially reversing T cell exhaustion. Herein, we show that the ectonucleotidse CD39 is a marker of exhausted CD8+ T cells. CD8+ T cells specific for HCV or HIV express high levels of CD39, but those specific for EBV and CMV do not. CD39 expressed by CD8+ T cells in chronic infection is enzymatically active, co-expressed with PD-1, marks cells with a transcriptional signature of T cell exhaustion and correlates with viral load in HIV and HCV. In the mouse model of chronic Lymphocytic Choriomeningitis Virus infection, virus-specific CD8+ T cells contain a population of CD39high CD8+ T cells that is absent in functional memory cells elicited by acute infection. This CD39high CD8+ T cell population is enriched for cells with the phenotypic and functional profile of terminal exhaustion. These findings provide a new marker of T cell exhaustion, and implicate the purinergic pathway in the regulation of T cell exhaustion. |
| spellingShingle | Gupta, P Godec, J Wolski, D Adland, E Yates, K Pauken, K Cosgrove, C Ledderose, C Junger, W Robson, S Wherry, E Alter, G Goulder, P Klenerman, P Sharpe, A Lauer, G Haining, W CD39 Expression identifies terminally exhausted CD8+ T cells |
| title | CD39 Expression identifies terminally exhausted CD8+ T cells |
| title_full | CD39 Expression identifies terminally exhausted CD8+ T cells |
| title_fullStr | CD39 Expression identifies terminally exhausted CD8+ T cells |
| title_full_unstemmed | CD39 Expression identifies terminally exhausted CD8+ T cells |
| title_short | CD39 Expression identifies terminally exhausted CD8+ T cells |
| title_sort | cd39 expression identifies terminally exhausted cd8 t cells |
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