title: Bcl6 expressing follicular helper CD4 T cells are fate committed early and have the capacity to form memory.
abstract: Follicular helper CD4 T (Tfh) cells are a distinct type of differentiated CD4 T cells uniquely specialized for B cell help. In this study, we examined Tfh cell fate commitment, including distinguishing features of Tfh versus Th1 proliferation and survival. Using cell transfer approaches at early time points after an acute viral infection, we demonstrate that early Tfh cells and Th1 cells are already strongly cell fate committed by day 3. Nevertheless, Tfh cell proliferation was tightly regulated in a TCR-dependent manner. The Tfh cells still depend on extrinsic cell fate cues from B cells in their physiological in vivo environment. Unexpectedly, we found that Tfh cells share a number of phenotypic parallels with memory precursor CD8 T cells, including selective upregulation of IL-7Rα and a collection of coregulated genes. As a consequence, the early Tfh cells can progress to robustly form memory cells. These data support the hypothesis that CD4 and CD8 T cells share core aspects of a memory cell precursor gene expression program involving Bcl6, and a strong relationship exists between Tfh cells and memory CD4 T cell development.
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors.forename: Youn Soo
authors.initials: YS
authors.lastname: Choi
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Yang
authors.forename: Isharat
authors.initials: I
authors.lastname: Yusuf
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Johnston
authors.forename: Jason
authors.initials: J
authors.lastname: Greenbaum
authors.forename: Bjoern
authors.initials: B
authors.lastname: Peters
authors.forename: Shane
authors.initials: S
authors.lastname: Crotty
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D007156:Immunologic Memory; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D054380:Receptors, CXCR5 / Q000096:biosynthesis / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation
chemical_list: C490010:Bcl6 protein, mouse; C513179:CXCR5 protein, mouse; D004268:DNA-Binding Proteins; D011498:Protein Precursors; D051560:Proto-Oncogene Proteins c-bcl-6; D054380:Receptors, CXCR5