title: CD127+CCR5+CD38+++ CD4+ Th1 effector cells are an early component of the primary immune response to vaccinia virus and precede development of interleukin-2+ memory CD4+ T cells.
abstract: The stages of development of human antigen-specific CD4+ T cells responding to viral infection and their differentiation into long-term memory cells are not well understood. The inoculation of healthy adults with vaccinia virus presents an opportunity to study these events intensively. Between days 11 and 14 postinoculation, there was a peak of proliferating CCR5+CD38+++ CD4+ effector cells which contained the cytotoxic granule marker T-cell intracellular antigen 1 and included gamma interferon (IFN-gamma)-producing vaccinia virus-specific CD4+ T cells. The majority of these initial vaccinia virus-specific CD4+ T cells were CD127+ and produced interleukin-2 (IL-2) but not CTLA-4 in response to restimulation in vitro. Between days 14 and 21, there was a switch from IFN-gamma and IL-2 coexpression to IL-2 production only, coinciding with a resting phenotype and an increased in vitro proliferation response. The early CCR5+CD38+++ vaccinia virus-specific CD4+ T cells were similar to our previous observations of human immunodeficiency virus (HIV)-specific CD4+ T cells in primary HIV type 1 (HIV-1) infection, but the vaccinia virus-specific cells expressed much more CD127 and IL-2 than we previously found in their HIV-specific counterparts. The current study provides important information on the differentiation of IL-2+ vaccinia virus-specific memory cells, allowing further study of antiviral effector CD4+ T cells in healthy adults and their dysfunction in HIV-1 infection.
authors.affiliation: Centre for Immunology, St. Vincent's Hospital, Victoria Street, Darlinghurst, NSW 2010, Australia. j.zaunders@cfi.unsw.edu.au
authors.forename: John J
authors.initials: JJ
authors.lastname: Zaunders
authors.forename: Wayne B
authors.initials: WB
authors.lastname: Dyer
authors.forename: Mee Ling
authors.initials: ML
authors.lastname: Munier
authors.forename: Susanna
authors.initials: S
authors.lastname: Ip
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Amyes
authors.forename: William
authors.initials: W
authors.lastname: Rawlinson
authors.forename: Robert
authors.initials: R
authors.lastname: De Rose
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kent
authors.forename: John S
authors.initials: JS
authors.lastname: Sullivan
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Kelleher
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000328:Adult; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D060908:CTLA-4 Antigen; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000032:analysis; D008297:Male; D039102:Poly(A)-Binding Proteins / Q000032:analysis; D019713:Receptors, CCR5 / Q000032:analysis; D020395:Receptors, Interleukin-7 / Q000032:analysis; D012900:Smallpox Vaccine / Q000008:administration & dosage / Q000276:immunology; D000074019:T-Cell Intracellular Antigen-1; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D013997:Time Factors; D014616:Vaccinia virus / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C078786:DryVax vaccine; D007376:Interleukin-2; D039102:Poly(A)-Binding Proteins; D019713:Receptors, CCR5; D020395:Receptors, Interleukin-7; D012900:Smallpox Vaccine; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D007371:Interferon-gamma; D051997:ADP-ribosyl Cyclase 1