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

dc.creatorTonnerre, Pierre
dc.creatorWolski, David
dc.creatorSubudhi, Sonu
dc.creatorAl-Jabban, Jihad
dc.creatorHoogeveen, Ruben C.
dc.creatorDamasio, Marcos
dc.creatorDrescher, Hannah K.
dc.creatorBartsch, Lea M.
dc.creatorTully, Damien C.
dc.creatorSen, Debattama R.
dc.creatorBean, David J.
dc.creatorBrown, Joelle
dc.creatorTorres-Cornejo, Almudena
dc.creatorRobidoux, Maxwell
dc.creatorKvistad, Daniel
dc.creatorAlatrakchi, Nadia
dc.creatorCui, Ang
dc.creatorLieb, David
dc.creatorCheney, James A.
dc.creatorGustafson, Jenna
dc.creatorLewis-Ximenez, Lia L.
dc.creatorMassenet-Regad, Lucile
dc.creatorEisenhaure, Thomas
dc.creatorAneja, Jasneet
dc.creatorHaining, W. Nicholas
dc.creatorChung, Raymond T.
dc.creatorHacohen, Nir
dc.creatorAllen, Todd M.
dc.creatorKim, Arthur Y.
dc.creatorLauer, Georg M.
dc.date2021-11-07T15:47:07Z
dc.date2021-11-07T15:47:07Z
dc.date2021
dc.date.accessioned2023-09-26T20:36:07Z
dc.date.available2023-09-26T20:36:07Z
dc.identifierTONNERRE, Pierre et al. Differentiation of exhausted CD8 T cells after termination of chronic antigen stimulation stops short of achieving functional T cell memory. bioRxiv preprint, p. 1-49, Apr. 2021.
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/49718
dc.identifier10.1101/2021.04.03.437705
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8860376
dc.descriptionT 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. Analysis of antigen-specific CD8+ T cells before and after antigen removal in human hepatitis C virus (HCV) infection confirmed pervasive phenotypic, functional, and transcriptional differences between exhausted and memory CD8+ T cells. After viral cure, we observed broad phenotypic and transcriptional changes in clonally stable exhausted T-cell populations suggesting differentiation towards 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 shorter periods of time because of viral escape mutations were functionally and transcriptionally more similar to memory T cells from spontaneously resolved acute HCV infection. Thus, duration of T cell stimulation impacts the ability to recover from exhaustion, as antigen removal after long-term T cell exhaustion is insufficient for the development of key T cell memory characteristics.
dc.formatapplication/pdf
dc.languageeng
dc.publisherbioRxiv
dc.rightsrestricted access
dc.subjectExaustão de células T
dc.subjectRecuperação imunológica
dc.subjectInfecção por HCV
dc.subjectTerapia antiviral
dc.subjectT cell exhaustion
dc.subjectImmunological recovery
dc.subjectHCV infection
dc.subjectAntiviral therapy
dc.titleDifferentiation of exhausted CD8 T cells after termination of chronic antigen stimulation stops short of achieving functional T cell memory
dc.typePreprint


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