Epigenetic scars of CD8+ T cell exhaustion persist after cure of chronic infection in humans
T cell exhaustion is an induced state of dysfunction that arises in response to chronic infection and cancer. Exhausted CD8 + T cells acquire a distinct epigenetic state, but it is not known whether that chromatin landscape is fixed or plastic following the resolution of a chronic infection. Here we...
Uložené v:
| Vydané v: | Nature immunology Ročník 22; číslo 8; s. 1020 - 1029 |
|---|---|
| Hlavní autori: | , , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
| Vydavateľské údaje: |
New York
Nature Publishing Group US
01.08.2021
Nature Publishing Group |
| Predmet: | |
| ISSN: | 1529-2908, 1529-2916, 1529-2916 |
| On-line prístup: | Získať plný text |
| Tagy: |
Pridať tag
Žiadne tagy, Buďte prvý, kto otaguje tento záznam!
|
| Shrnutí: | T cell exhaustion is an induced state of dysfunction that arises in response to chronic infection and cancer. Exhausted CD8
+
T cells acquire a distinct epigenetic state, but it is not known whether that chromatin landscape is fixed or plastic following the resolution of a chronic infection. Here we show that the epigenetic state of exhaustion is largely irreversible, even after curative therapy. Analysis of chromatin accessibility in HCV- and HIV-specific responses identifies a core epigenetic program of exhaustion in CD8
+
T cells, which undergoes only limited remodeling before and after resolution of infection. Moreover, canonical features of exhaustion, including super-enhancers near the genes
TOX
and
HIF1A
, remain ‘epigenetically scarred.’ T cell exhaustion is therefore a conserved epigenetic state that becomes fixed and persists independent of chronic antigen stimulation and inflammation. Therapeutic efforts to reverse T cell exhaustion may require new approaches that increase the epigenetic plasticity of exhausted T cells.
The degree of plasticity in the epigenetic landscape of exhausted T cells has been unclear. Sen and colleagues find that exhausted CD8
+
T cells demonstrate a stable core epigenetic exhaustion signature that persists independent of inflammation or viral antigen. |
|---|---|
| Bibliografia: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 These authors contributed equally. Author Contributions D.R.S. and W.N.H. conceived of the study and designed the experiments. D.R.S., K.B.Y., G.E.M., U.G., R.A., D.E.C., S.A.W. performed experiments and/or data analysis. P.T., D.W., D.C.T., R.T.C., T.A., A.Y.K., G.M.L. contributed to the HCV clinical trial design, patient recruitment, sample processing, viral sequencing studies and/or transcriptional analysis. G.E.M., S.F., J. Frater., J. Fox contributed to the HIV clinical trial design, patient recruitment, and/or sample processing. D.R.S. and W.N.H. wrote the manuscript; all authors reviewed and edited the manuscript. |
| ISSN: | 1529-2908 1529-2916 1529-2916 |
| DOI: | 10.1038/s41590-021-00979-1 |