title: T cells maintain an exhausted phenotype after antigen withdrawal and population reexpansion.
abstract: During chronic infection, pathogen-specific CD8(+) T cells upregulate expression of molecules such as the inhibitory surface receptor PD-1, have diminished cytokine production and are thought to undergo terminal differentiation into exhausted cells. Here we found that T cells with memory-like properties were generated during chronic infection. After transfer into naive mice, these cells robustly proliferated and controlled a viral infection. The reexpanded T cell populations continued to have the exhausted phenotype they acquired during the chronic infection. Thus, the cells underwent a form of differentiation that was stably transmitted to daughter cells. We therefore propose that during persistent infection, effector T cells stably differentiate into a state that is optimized to limit viral replication without causing overwhelming immunological pathology.
authors: Swiss Vaccine Research Institute, Epalinges, Switzerland.
authors: Daniel T
authors: DT
authors: Utzschneider
authors: Amandine
authors: A
authors: Legat
authors: Silvia A
authors: SA
authors: Fuertes Marraco
authors: Lucie
authors: L
authors: Carrié
authors: Immanuel
authors: I
authors: Luescher
authors: Daniel E
authors: DE
authors: Speiser
authors: Dietmar
authors: D
authors: Zehn
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002908:Chronic Disease; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology*; D016130:Immunophenotyping; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000956:Antigens, Viral; D061026:Programmed Cell Death 1 Receptor; D016693:Receptors, Antigen, T-Cell, alpha-beta
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