title: Effector CD4 T-cell transition to memory requires late cognate interactions that induce autocrine IL-2.
abstract: It is unclear how CD4 T-cell memory formation is regulated following pathogen challenge, and when critical mechanisms act to determine effector T-cell fate. Here, we report that following influenza infection most effectors require signals from major histocompatibility complex class II molecules and CD70 during a late window well after initial priming to become memory. During this timeframe, effector cells must produce IL-2 or be exposed to high levels of paracrine or exogenously added IL-2 to survive an otherwise rapid default contraction phase. Late IL-2 promotes survival through acute downregulation of apoptotic pathways in effector T cells and by permanently upregulating their IL-7 receptor expression, enabling IL-7 to sustain them as memory T cells. This new paradigm defines a late checkpoint during the effector phase at which cognate interactions direct CD4 T-cell memory generation.
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655, USA.
authors.forename: K Kai
authors.initials: KK
authors.lastname: McKinstry
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655, USA.
authors.forename: Tara M
authors.initials: TM
authors.lastname: Strutt
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655, USA.
authors.forename: Bianca
authors.initials: B
authors.lastname: Bautista
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655, USA.
authors.forename: Wenliang
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Kuang
authors.affiliation: Trudeau Institute, 154 Algonquin Avenue, Saranac Lake, New York 12983, USA.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Cooper
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Swain
mesh_terms: D000818:Animals; D017209:Apoptosis; D019898:Autocrine Communication; D053282:CD27 Ligand / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005802:Genes, MHC Class II; D007156:Immunologic Memory; D009980:Influenza A virus / Q000276:immunology*; D007376:Interleukin-2 / Q000378:metabolism*; D015851:Interleukin-7 / Q000378:metabolism*; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism
chemical_list: D053282:CD27 Ligand; C505771:CD70 protein, human; D007376:Interleukin-2; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C576410:interleukin-7, mouse