title: TCF1 Is Required for the T Follicular Helper Cell Response to Viral Infection.
abstract: T follicular helper (TFH) and T helper 1 (Th1) cells generated after viral infections are critical for the control of infection and the development of immunological memory. However, the mechanisms that govern the differentiation and maintenance of these two distinct lineages during viral infection remain unclear. We found that viral-specific TFH and Th1 cells showed reciprocal expression of the transcriptions factors TCF1 and Blimp1 early after infection, even before the differential expression of the canonical TFH marker CXCR5. Furthermore, TCF1 was intrinsically required for the TFH cell response to viral infection; in the absence of TCF1, the TFH cell response was severely compromised, and the remaining TCF1-deficient TFH cells failed to maintain TFH-associated transcriptional and metabolic signatures, which were distinct from those in Th1 cells. Mechanistically, TCF1 functioned through forming negative feedback loops with IL-2 and Blimp1. Our findings demonstrate an essential role of TCF1 in TFH cell responses to viral infection.
authors.affiliation: National Human Genome Research Institute (NHGRI), NIH, Bethesda, MD 20892, USA. Electronic address: tuoqiwu@gmail.com.
authors.forename: Tuoqi
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Hyun Mu
authors.initials: HM
authors.lastname: Shin
authors.affiliation: National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, MD 20892, USA.
authors.forename: E Ashley
authors.initials: EA
authors.lastname: Moseman
authors.affiliation: National Cancer Institute (NCI), NIH, Bethesda, MD 20892, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ji
authors.affiliation: National Human Genome Research Institute (NHGRI), NIH, Bethesda, MD 20892, USA.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Huang
authors.affiliation: National Cancer Institute (NCI), NIH, Bethesda, MD 20892, USA.
authors.forename: Christelle
authors.initials: C
authors.lastname: Harly
authors.affiliation: National Institute on Aging (NIA), NIH, Baltimore, MD 21224, USA.
authors.forename: Jyoti M
authors.initials: JM
authors.lastname: Sen
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Berg
authors.affiliation: National Cancer Institute (NCI), NIH, Bethesda, MD 20892, USA.
authors.forename: Luca
authors.initials: L
authors.lastname: Gattinoni
authors.affiliation: National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, MD 20892, USA.
authors.forename: Dorian B
authors.initials: DB
authors.lastname: McGavern
authors.affiliation: National Human Genome Research Institute (NHGRI), NIH, Bethesda, MD 20892, USA. Electronic address: pams@nhgri.nih.gov.
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Schwartzberg
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D018858:Germinal Center / Q000276:immunology* / Q000473:pathology / Q000821:virology; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics / Q000276:immunology*; D054884:Host-Pathogen Interactions; D007156:Immunologic Memory; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000074462:Positive Regulatory Domain I-Binding Factor 1; D054380:Receptors, CXCR5 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology / Q000637:transplantation / Q000821:virology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*; D014158:Transcription, Genetic
chemical_list: C513179:CXCR5 protein, mouse; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; D007376:Interleukin-2; C513258:Prdm1 protein, mouse; D054380:Receptors, CXCR5; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1