title: Viral persistence redirects CD4 T cell differentiation toward T follicular helper cells.
abstract: CD4 T cell responses are crucial to prevent and control viral infection; however, virus-specific CD4 T cell activity is considered to be rapidly lost during many persistent viral infections. This is largely caused by the fact that during viral persistence CD4 T cells do not produce the classical Th1 cytokines associated with control of acute viral infections. Considering that CD4 T cell help is critical for both CD8 T cell and B cell functions, it is unclear how CD4 T cells can lose responsiveness but continue to sustain long-term control of persistent viral replication. We now demonstrate that CD4 T cell function is not extinguished as a result of viral persistence. Instead, viral persistence and prolonged T cell receptor stimulation progressively redirects CD4 T cell development away from the Th1 response induced during an acute infection toward T follicular helper cells. Importantly, this sustained CD4 T cell functionality is critical to maintain immunity and ultimately aid in the control of persistent viral infection.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Fahey
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Wilson
authors.forename: Heidi
authors.initials: H
authors.lastname: Elsaesser
authors.forename: Chris D
authors.initials: CD
authors.lastname: Fistonich
authors.forename: Dorian B
authors.initials: DB
authors.lastname: McGavern
authors.forename: David G
authors.initials: DG
authors.lastname: Brooks
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines