Details

Autor(en) / Beteiligte

• Tonnerre, Pierre
• Wolski, David
• Subudhi, Sonu
• Aljabban, Jihad
• Hoogeveen, Ruben C
• Damasio, Marcos
• Drescher, Hannah K
• Bartsch, Lea M
• Tully, Damien C
• Sen, Debattama R
• Bean, David J
• Brown, Joelle
• Torres-Cornejo, Almudena
• Robidoux, Maxwell
• Kvistad, Daniel
• Alatrakchi, Nadia
• Cui, Ang
• Lieb, David
• Cheney, James A
• Gustafson, Jenna
• Lewis-Ximenez, Lia L
• Massenet-Regad, Lucile
• Eisenhaure, Thomas
• Aneja, Jasneet
• Haining, W Nicholas
• Chung, Raymond T
• Hacohen, Nir
• Allen, Todd M
• Kim, Arthur Y
• Lauer, Georg M

Titel

Differentiation of exhausted CD8 + T cells after termination of chronic antigen stimulation stops short of achieving functional T cell memory

Ist Teil von

• Nature immunology, 2021-08, Vol.22 (8), p.1030

Ort / Verlag

United States

Erscheinungsjahr

2021

Link zum Volltext

Beschreibungen/Notizen

• T cell exhaustion is associated with failure to clear chronic infections and malignant cells. Defining the molecular mechanisms of T cell exhaustion and reinvigoration is essential to improving immunotherapeutic modalities. Here we confirmed pervasive phenotypic, functional and transcriptional differences between memory and exhausted antigen-specific CD8 T cells in human hepatitis C virus (HCV) infection before and after treatment. After viral cure, phenotypic changes in clonally stable exhausted T cell populations suggested differentiation toward a memory-like profile. However, functionally, the cells showed little improvement, and critical transcriptional regulators remained in the exhaustion state. Notably, T cells from chronic HCV infection that were exposed to antigen for less time because of viral escape mutations were functionally and transcriptionally more similar to memory T cells from spontaneously resolved HCV infection. Thus, the duration of T cell stimulation impacts exhaustion recovery, with antigen removal after long-term exhaustion being insufficient for the development of functional T cell memory.