title: Transcription Factor Bcl11b Controls Effector and Memory CD8 T cell Fate Decision and Function during Poxvirus Infection.
abstract: CD8+T cells play an important role in host resistance to many viral infections, but the underlying transcriptional mechanisms governing their differentiation and functionality remain poorly defined. By using a highly virulent systemic and respiratory poxvirus infection in mice, we show that the transcription factor Bcl11b provides a dual trigger that sustains the clonal expansion of virus-specific effector CD8+T cells, while simultaneously suppressing the expression of surface markers associated with short-lived effector cell (SLEC) differentiation. Additionally, we demonstrate that Bcl11b supports the acquisition of memory precursor effector cell (MPEC) phenotype and, thus, its absence causes near complete loss of lymphoid and lung-resident memory cells. Interestingly, despite having normal levels of T-bet and Eomesodermin, Bcl11b-deficient CD8+T cells failed to execute effector differentiation needed for anti-viral cytokine production and degranulation, suggesting a non-redundant role of Bcl11b in regulation of this program. Thus, Bcl11b is a critical player in fate decision of SLECs and MPECs, as well as effector function and memory formation.
authors: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida , Gainesville, FA , USA.
authors: Georges
authors: G
authors: Abboud
authors: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida , Gainesville, FA , USA.
authors: Jessica
authors: J
authors: Stanfield
authors: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida , Gainesville, FA , USA.
authors: Vikas
authors: V
authors: Tahiliani
authors: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida , Gainesville, FA , USA.
authors: Pritesh
authors: P
authors: Desai
authors: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida , Gainesville, FA , USA.
authors: Tarun E
authors: TE
authors: Hutchinson
authors: Department of Medicine, Division of Pulmonary Medicine, College of Medicine, University of Florida , Gainesville, FA , USA.
authors: Kyle J
authors: KJ
authors: Lorentsen
authors: Department of Medicine, Division of Pulmonary Medicine, College of Medicine, University of Florida , Gainesville, FA , USA.
authors: Jonathan J
authors: JJ
authors: Cho
authors: Department of Medicine, Division of Pulmonary Medicine, College of Medicine, University of Florida , Gainesville, FA , USA.
authors: Dorina
authors: D
authors: Avram
authors: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida , Gainesville, FA , USA.
authors: Shahram
authors: S
authors: Salek-Ardakani
keywords: BCL11b; T cells; lung; memory; poxvirus; transcription factors; viral