title: Short-Lived Antigen Recognition but Not Viral Infection at a Defined Checkpoint Programs Effector CD4 T Cells To Become Protective Memory.
abstract: Although memory CD4 T cells are critical for effective immunity to pathogens, the mechanisms underlying their generation are still poorly defined. We find that following murine influenza infection, most effector CD4 T cells undergo apoptosis unless they encounter cognate Ag at a defined stage near the peak of effector generation. Ag recognition at this memory checkpoint blocks default apoptosis and programs their transition to long-lived memory. Strikingly, we find that viral infection is not required, because memory formation can be restored by the addition of short-lived, Ag-pulsed APC at this checkpoint. The resulting memory CD4 T cells express an enhanced memory phenotype, have increased cytokine production, and provide protection against lethal influenza infection. Finally, we find that memory CD4 T cell formation following cold-adapted influenza vaccination is boosted when Ag is administered during this checkpoint. These findings imply that persistence of viral Ag presentation into the effector phase is the key factor that determines the efficiency of memory generation. We also suggest that administering Ag at this checkpoint may improve vaccine efficacy.
authors: Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01605.
authors: Bianca L
authors: BL
authors: Bautista
authors: Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01605.
authors: Priyadharshini
authors: P
authors: Devarajan
authors: Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01605.
authors: K Kai
authors: KK
authors: McKinstry
authors: Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01605.
authors: Tara M
authors: TM
authors: Strutt
authors: Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01605.
authors: Allen M
authors: AM
authors: Vong
authors: Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01605.
authors: Michael C
authors: 0000-0002-5986-5426
authors: MC
authors: Jones
authors: Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01605.
authors: Yi
authors: 0000-0002-3266-1781
authors: Y
authors: Kuang
authors: Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01605.
authors: Daniel
authors: 0000-0003-0547-817X
authors: D
authors: Mott
authors: Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01605 Susan.Swain@umassmed.edu.
authors: Susan L
authors: 0000-0002-3643-8018
authors: SL
authors: Swain
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D018816:Genes, cdc; D006801:Humans; D007156:Immunologic Memory; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D009975:Orthomyxoviridae / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology
chemical_list: D000956:Antigens, Viral; D016207:Cytokines; D007252:Influenza Vaccines; D007371:Interferon-gamma